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1.
Nanoscale ; 13(34): 14417-14425, 2021 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-34473184

RESUMEN

The recurrence and metastasis of tumor after surgery is the main cause of death for patients with breast cancer. Systemic chemotherapy suffered from low delivery efficiency to tumors and the side effects of chemo drugs. Localized chemotherapy using drug-containing implants is an alternative, while the reconstruction of breast tissue is generally considered after chemotherapy, resulting in a second surgery for patients. Here, we describe a strategy using implantable drug-containing polymeric scaffolds to deliver chemo drugs directly to the post-resection site, and simultaneously provide mechanical support and regenerative niche for breast tissue reconstruction. When doxorubicin was loaded in mesoporous silica nanoparticles and subsequently incorporated into polycaprolactone scaffolds (DMSN@PCL), a 9-week sustained drug release was achieved post implantation in mice. The local recurrence of residual tumor after surgery was significantly inhibited within 4 weeks in a post-surgical mouse model bearing xenograft MDA-MB-231 tumor. DMSN@PCL scaffolds exhibited good biocompatibility in mice during the treatment. We believe our strategy holds great promise as an adjuvant localized chemotherapy in clinics for combating post-resection breast cancer recurrence.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Nanopartículas , Animales , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Doxorrubicina/uso terapéutico , Femenino , Humanos , Ratones , Poliésteres
2.
Mater Sci Eng C Mater Biol Appl ; 128: 112261, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34474820

RESUMEN

Glioblastoma multiforme (GBM) remains a major cause of mortality because treatments are precluded by to the limited transport and penetration of chemotherapeutics across the blood-brain barrier. Pitavastatin (PTV) is a hydrophobic Food and Drug Administration (FDA)-approved anticholesterolemic agent with reported anti-GBM activity. In the present study, we encapsulate PTV in silica-coated polymeric micelles (SiO2 PMs) surface-modified with the cyclic peptide Arg-Gly-Asp-Phe-Val (cRGDfV) that actively targets the αvß3 integrin overexpressed in the BBB endothelium and GBM. A central composite design is utilized to optimize the preparation process and improve the drug encapsulation ratio from 131 to 780 µg/mL. The silica shell provides full colloidal stability upon extreme dilution and enables a better control of the release kinetics in vitro with 28% of the cargo released after 12 h. Furthermore, SiO2 PMs show excellent compatibility and are internalized by human BBB endothelial cells, astrocytes and pericytes, as shown by confocal laser scanning fluorescence microscopy and flow cytometry. Finally, the anticancer efficacy is assessed in a pediatric patient-derived glioma cell line expressing high levels of the integrin subunits αv, ß3 and ß5. This PTV-loaded nanocarrier triggers apoptosis by reducing the mRNA level of anti-apoptotic genes NF-kß, IL-6, BIRC1 and BIRC5 by 89%, 33%, 81% and 63%, respectively, and the cell viability by >60%. Overall, our results suggest the potential of these hybrid nanocarriers for the targeted therapy of GBM and other tumors overexpressing integrin receptors.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/tratamiento farmacológico , Línea Celular Tumoral , Niño , Células Endoteliales , Glioblastoma/tratamiento farmacológico , Humanos , Integrinas , Micelas , Dióxido de Silicio
3.
Mater Sci Eng C Mater Biol Appl ; 128: 112311, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34474862

RESUMEN

Herein, we design a rGO-based magnetic nanocomposite by decorating rGO with citrate-coated magnetic nanoparticles (CMNP). The magnetic rGO (mrGO) was modified by phospholipid-polyethylene glycol to prepare PEGylated mrGO, for conjugating with gastrin-releasing peptide receptor (GRPR)-binding peptide (mrGOG). The anticancer drug doxorubicin (DOX) was bound to mrGO (mrGOG) by π-π stacking for drug delivery triggered by the low pH value in the endosome. The mrGOG showed enhanced photothermal effect under NIR irradiation, endorsing its role for dual targeted DOX delivery. With efficient DOX release in the endosomal environment and heat generation from light absorption in the NIR range, mrGOG/DOX could be used for combination chemo-photothermal therapy after intracellular uptake by cancer cells. We characterized the physico-chemical as well as biological properties of the synthesized nanocomposites. The mrGOG is stable in biological buffer solution, showing high biocompatibility and minimum hemolytic properties. Using U87 glioblastoma cells, we confirmed the magnetic drug targeting effect in vitro for selective cancer cell killing. The peptide ligand-mediated targeted delivery increases the efficiency of intracellular uptake of both nanocomposite and DOX up to ~3 times due to the over-expressed GRPR on U87 surface, leading to higher cytotoxicity. The increased cytotoxicity using mrGOG over mrGO was shown from a decreased IC50 value (0.70 to 0.48 µg/mL) and an increased cell apoptosis rate (19.8% to 47.1%). The IC50 and apoptosis rate changed further to 0.19 µg/mL and 76.8% in combination with NIR laser irradiation, with the photothermal effect supported from upregulation of heat shock protein HSP70 expression. Using U87 tumor xenograft model created in nude mice, we demonstrated that magnetic guidance after intravenous delivery of mrGOG/DOX could significantly reduce tumor size and prolong animal survival over free DOX and non-magnetic guided groups. Augmented with NIR laser treatment for 5 min, the anti-cancer efficacy significantly improves with elevated cell apoptosis and reduced cell proliferation. Together with safety profiles from hematological as well as major organ histological analysis of treated animals, the mrGOG nanocomposite is an effective nanomaterial for combination chemo-photothermal cancer therapy.


Asunto(s)
Hipertermia Inducida , Nanocompuestos , Neoplasias , Animales , Línea Celular Tumoral , Doxorrubicina/farmacología , Liberación de Fármacos , Grafito , Fenómenos Magnéticos , Ratones , Ratones Desnudos , Fototerapia , Receptores de Bombesina
4.
Mater Sci Eng C Mater Biol Appl ; 128: 112341, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34474891

RESUMEN

In order to maximize the retention of the photodynamic therapy (PDT) efficacy, while avoiding the dilemma of hypoxia and high reducing substances in tumor tissue, fluoropolymers were synthesized in a simple and effective methods. Fluorous effect with good oxygen carrying capacity was endowed by the fluorine-containing section in fluoropolymers and the perfluorodecalin (PFD) together, the reaction site with GSH was provided by the disulfide bond, which enhanced PDT efficiency through the sequential "AND" logic gate design. Two kind of fluorine-containing nanocarriers (M-Ce6 and E-Ce6) were obtained by solvent evaporation or ultrasound emulsification with PFD, respectively. In vitro, both of them showed promising high ROS generation under photoirradiation. Benefiting by cavitation effects, E-Ce6 had a more significant statistical difference in cellular uptake. Furthermore, the cells incubating with E-Ce6 hardly were noticed that the hypoxia signal appeared under hypoxia, while reducing the intracellular GSH content by more than 15%. Through the sequential "AND" logic gate design, ROS production even under hypoxia and GSH conditions of E-Ce6 was also almost 1.5 times that of Ce6 under normoxia. Enhancing effect of E-Ce6 was 13.47 times and 6.85 times, while selectivity ratio reached 5.13 times and 4.81 times compared with Ce6 and M-Ce6. The two-pronged strategy showed a high potential for delivering the Ce6 to deep inside of cancer cells and killing it in the simulated tumor by PDT. These above results demonstrated the potential of E-Ce6, as oxygen self-sufficiency and GSH depletion nanocarriers for combined enhancement of photodynamic therapy.


Asunto(s)
Fotoquimioterapia , Porfirinas , Línea Celular Tumoral , Flúor , Oxígeno , Fármacos Fotosensibilizantes/farmacología
5.
J Egypt Natl Canc Inst ; 33(1): 24, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34486082

RESUMEN

BACKGROUND: Telomere dysfunction is one of the hallmarks of cancer and is crucial to prostate carcinogenesis. TERF1 is a gene essential to telomere maintenance, and its dysfunction has already been associates with several cancers. TERF1 is a target of miR-155, and this microRNA can inhibit its expression and promotes carcinogenesis in breast cancer. We aim to analyze TERF1, in gene and mRNA level, involvement in prostate cancer progression. RESULTS: Alterations in TERF1 DNA were evaluated using datasets of primary tumor and castration-resistant tumors (CRPC) deposited in cBioportal. The expression of TERF1 mRNA levels was assessed utilizing TCGA datasets, clinical specimens, and metastatic prostate cancer cell lines (LNCaP, DU145, and PC3). Six percent of localized prostate cancer presents alterations in TERF1 (the majority of that was amplifications). In the CRPC cohort, 26% of samples had TERF1 amplification. Patients with TERF1 alterations had the worst overall survival only on localized cancer cohort (p = 0.0027). In the TCGA cohort, mRNA levels of TERF1 were downregulated in comparison with normal tissue (p = 0.0013) and upregulated in tumors that invade lymph nodes (p = 0.0059). The upregulation of TERF1 is also associated with worst overall survival (p = 0.0028) and disease-free survival (p = 0.0023). There is a positive correlation between TERF1 and androgen receptor expression in cancer tissue (r = 0.53, p < 0.00001) but not on normal tissue (r = - 0.16, p = 0.12). In the clinical specimens, there is no detectable expression of TERF1 and upregulation of miR-155 (p = 0.0348). In cell lines, TERF1 expression was higher in LNCaP and was progressively lower in DU145 and PC3 (p = 0.0327) with no differences in miR-155 expression. CONCLUSION: Amplification/upregulation of TERF1 was associated with the worst prognostic in localized prostate cancer. Our results corroborate that miR-155 regulates TERF1 expression in prostate cancer. TERF1 has the potential to become a biomarker in prostate cancer.


Asunto(s)
MicroARNs , Neoplasias de la Próstata , Proteínas de Unión a Telómeros/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Pronóstico , Neoplasias de la Próstata/genética
6.
Nanoscale ; 13(29): 12553-12564, 2021 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-34477614

RESUMEN

Chemodynamic therapy (CDT), the ability to transform H2O2 into a highly toxic hydroxyl radical (˙OH) through a Fenton or Fenton like reaction to kill cancer cells, enables selective tumor therapy. However, the effect is seriously limited by the insufficiency of endogenous H2O2 in cancer cells. Additionally, the specific recognition of epitope imprinting plays an important role in targeting cancer cell markers. In this work, we prepared H2O2 self-supplying degradable epitope molecularly imprinted polymers (MIP) for effective CDT, employing fluorescent calcium peroxide (FCaO2) as an imaging probe and a source of H2O2, the exposed peptide in the CD47 extracellular region as the template, copper acrylate as one of the functional monomers and N,N'-bisacrylylcystamine (BAC) as a cross-linker. MIP with recognition sites can specifically target CD47-positive cancer cells to achieve fluorescence imaging. Under the reduction of glutathione (GSH), the MIP were degraded and the exposed FCaO2 reacted with water to continuously produce H2O2 in the slightly acidic environment in cancer cells. The self-supplied H2O2 produced ˙OH through a Fenton like catalytic reaction mediated by copper ions in the MIP framework, inducing cancer cell apoptosis. Therefore, the MIP nano-platform, which was capable of specific recognition of the cancer cell marker, H2O2 self-supply and controlled treatment, was successfully used for targeted CDT.


Asunto(s)
Peróxido de Hidrógeno , Polímeros , Línea Celular Tumoral , Epítopos , Imagen Óptica
7.
Nanoscale ; 13(32): 13735-13745, 2021 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-34477648

RESUMEN

Tumor radioresistance is a major issue in radiotherapy. To address it, a pH-responsive nanoradiosensitizer was synthesized employing a simple method. Initially, chloroplatinic acid was reduced by human serum albumin (HSA) to form HSA-wrapped Pt@HSA nanoparticles (NPs). Subsequently, cinnamicaldehyde (CA) was grafted on Pt@HSA via aldimine condensation to obtain nanoradiosensitizer Pt@HSA/CA NPs. CA would be released in tumor cells (pH = 5.5) to induce the production of reactive oxygen species, including H2O2, ˙OH, etc. The increased decomposition of H2O2 catalyzed by the NPs resulted in enhanced production of oxygen, leading to hypoxia relief of the tumor cells, which is beneficial for radiotherapy. Due to the high X-ray attenuation coefficient of Pt, Pt@HSA/CA NPs enhance the energy deposition of radiation. Cytotoxicity assay revealed that Pt@HSA/CA NPs resulted in a cell death rate of 77%, which was 24.4% higher than that of Pt@HSA NPs even under low-dose X-ray irradiation of 4 Gy. Colony formation assay demonstrated that the sensitization enhancement ratio was 1.37, indicating that Pt@HSA/CA NPs displayed remarkable radiosensitizing ability. Notably, in vivo results indicated that the NPs could increase the tumor inhibition rate to 91.2% with negligible side effects to normal tissues. These results demonstrate that Pt@HSA/CA NPs had outstanding tumor curative efficacy and hypotoxicity.


Asunto(s)
Peróxido de Hidrógeno , Nanopartículas , Línea Celular Tumoral , Humanos , Concentración de Iones de Hidrógeno , Estrés Oxidativo
8.
Nanoscale ; 13(33): 14049-14066, 2021 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-34477686

RESUMEN

Sonodynamic therapy (SDT) is a highly promising approach for cancer therapy, but its efficacy is severely hampered by the low specificity of sonosensitizers and the unfavorable characteristics of the tumor microenvironment (TME), such as hypoxia and glutathione (GSH) overexpression. To solve these problems, in this work, we encapsulated IR780 and MnO2 in PLGA and linked Angiopep-2 (Ang) to synthesize a multifunctional nanozyme (Ang-IR780-MnO2-PLGA, AIMP) to enhance SDT. With Ang functionalization to facilitate blood-brain barrier (BBB) penetration and glioma targeting, and through the function of IR780, these nanoparticles (NPs) showed improved targeting of cancer cells, especially mitochondria, and spread deep into tumor centers. Upon low-intensity focused ultrasound (LIFU) irradiation, reactive oxygen species (ROS) were produced and induced tumor cell apoptosis. Combined with the specific mitochondria-targeting ability of IR780, the sonodynamic effects were amplified because mitochondria are sensitive to ROS. In addition, MnO2 exhibited enzyme-like activity, reacting with the high levels of hydrogen protons (H+), H2O2 and GSH in the TME to continuously produce oxygen and consume GSH, which further enhanced the effect of SDT. Moreover, Mn2+ can be released in response to TME stimulation and used as a magnetic resonance (MR) contrast agent. In addition, IR780 has photoacoustic (PA)/fluorescence (FL) imaging capabilities. Our results demonstrated that AIMP NPs subjected to LIFU triggering maximally enhanced the therapeutic effect of SDT by multiple mechanisms, including multiple targeting, deep penetration, oxygen supply in situ and GSH depletion, thereby significantly inhibiting tumor growth and distal metastasis without systemic toxicity. In summary, this multifunctional nanozyme provides a promising strategy for cancer diagnosis and treatment under the intelligent guidance of multimodal imaging (PA/FL/MR) and may be a safe clinical translational method.


Asunto(s)
Nanopartículas , Terapia por Ultrasonido , Línea Celular Tumoral , Peróxido de Hidrógeno , Compuestos de Manganeso/farmacología , Imagen Multimodal , Óxidos , Microambiente Tumoral
9.
Nanoscale ; 13(31): 13231-13240, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34477731

RESUMEN

Although artemisinin (ART) has shown initial promise in cancer therapy, its therapeutic efficacy is limited by its low tumor inhibitory efficacy and unfavorable distribution. Considering the important role of heme in the specific parasite-killing effect of ART, we designed a liposomal nanostructure self-assembled from hemin-lipid (Hemesome) to co-deliver ART and hemin for cancer therapy. The synergistic chemotherapeutic and immunotherapeutic effects of hemin and ART were demonstrated both in vitro and in vivo. The liposome-like structure was relatively stable in the blood circulation and gastrointestinal tract environment, but dissociated in the tumor cell environment. The folic acid (FA) modification not only increased their efficiency for transport across the epithelium, but also increased their tumor accumulation. In mouse models, following oral administration of FA-Hemesome-ART nanoparticles (5 mg kg-1 ART in total) every other day and intraperitoneal injection with a programmed death-ligand 1 antibody (aPD-L1, 70 µg per mouse in total), MC38 tumors were completely inhibited within 30 days. The cured mice remained tumor-free 30 days after rechallenging them with another inoculation of MC38 cells due to the strong immune memory effect.


Asunto(s)
Artemisininas , Nanopartículas , Neoplasias , Animales , Línea Celular Tumoral , Hemina , Inmunoterapia , Lípidos , Ratones , Neoplasias/tratamiento farmacológico
10.
Nanoscale ; 13(31): 13328-13343, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34477739

RESUMEN

Facing the barriers in each step of the in vivo delivery cascade, the low drug delivery efficiency remains problematic in tumor therapy. Although recently the nanofibril drug delivery systems have shown improved circulation and accumulation compared with nanoparticles, the poor deep penetration and cellular internalization hinder their application, especially for pancreatic cancer with dense stroma. To comprehensively address the hurdles in the delivery cascade, a matrix metalloproteinase 2 (MMP-2) responsive transformable beaded nanofibril, which integrates the merits of nanofibril and small-sized nanoparticles, is established. The beaded nanofibril (GD@PPF) is prepared by conjugating gemcitabine-loaded small-sized nanoparticles (GD) with fibrous PEG-PCL (PPF) via GPLGVRG, a substrate peptide of MMP-2. GD@PPF escapes the clearance of the reticuloendothelial system (RES), prolongs the circulation time, and increases the selective accumulation in the tumor as fibrous micelles. Once accumulated in the tumor, small positively-charged GD is released from the beaded nanofibrils in response to MMP-2 overexpression in the stroma of pancreatic cancer, enabling permeation in the dense tumor matrix and cellular internalization, which makes up for the shortcomings of fibrous micelles. Furthermore, the remaining fibrous PPF surround the tumor tightly to impede the efflux of drugs, leading to improved retention. GD@PPF is biocompatible and exhibits excellent antitumor effect in Pan 02 subcutaneous tumor models. Therefore, the MMP-2 responsive transformable beaded nanofibril, which enhances the delivery efficiency in multiple stage of the delivery cascade, presents a promising strategy for pancreatic cancer therapy.


Asunto(s)
Nanopartículas , Neoplasias Pancreáticas , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Humanos , Metaloproteinasa 2 de la Matriz , Micelas , Neoplasias Pancreáticas/tratamiento farmacológico
11.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2878-2889, 2021 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-34472305

RESUMEN

In canonical Wnt/ß-catenin signaling pathway, ß-catenin/TCF4 (T-cell factor 4) interaction plays an important role in the pathogenesis and development of non-small cell lung cancer (NSCLC), and it is tightly associated with the proliferation, chemoresistance, recurrence and metastasis of NSCLC. Therefore, suppressing ß-catenin/TCF4 interaction in Wnt/ß-catenin signaling pathway would be a new therapeutic avenue against NSCLC metastasis. In this study, considering the principle of enzyme-linked immunosorbent assay (ELISA), an optimized high-throughput screening (HTS) assay was developed for the discovery of ß-catenin/TCF4 interaction antagonists. Subsequently, this ELISA-like screening assay was performed using 2 µg/mL GST-TCF4 ßBD and 0.5 µg/mL ß-catenin, then a high Z' factor of 0.83 was achieved. A pilot screening of a natural product library using this ELISA-like screening assay identified plumbagin as a potential ß-catenin/TCF4 interaction antagonist. Plumbagin remarkably inhibited the proliferation of A549, H1299, MCF7 and SW480 cell lines. More importantly, plumbagin significantly suppressed the ß-catenin-responsive transcription in TOPFlash assay. In short, this newly developed ELISA-like screening assay will be vital for the rapid screening of novel Wnt inhibitors targeting ß-catenin/TCF4 interaction, and this interaction is a potential anticancer target of plumbagin in vitro.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Factor de Transcripción 4/antagonistas & inhibidores , beta Catenina/antagonistas & inhibidores , Línea Celular Tumoral , Ensayo de Inmunoadsorción Enzimática , Ensayos Analíticos de Alto Rendimiento , Humanos , Factor de Transcripción 4/genética , beta Catenina/genética
12.
Nanoscale ; 13(31): 13473-13486, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34477752

RESUMEN

BACKGROUND: Currently, limited tumor drug permeation, poor oxygen perfusion and immunosuppressive microenvironments are the most important bottlenecks that significantly reduce the efficacy of photodynamic therapy (PDT). The main cause of these major bottlenecks is the platelet activation maintained abnormal tumor vessel barriers. Thus, platelet inhibition may present a new way to most effectively enhance the efficacy of PDT. However, to the best of our knowledge, few studies have validated the effectiveness of such a way in enhancing the efficacy of PDT both in vivo and in vitro. In this study, perfluoro-N-(4-methylcyclohexyl) piperidine-loaded albumin (PMP@Alb) nanoparticles were discovered, which possess excellent platelet inhibition ability. After PMP@Alb treatment, remarkably enhanced intra-tumoral drug accumulation, oxygen perfusion and T cell infiltration could be observed owing to the disrupted tumor vessel barriers. Besides, the effect of ICG@Lip mediated PDT was significantly amplified by PMP@Alb nanoparticles. It was demonstrated that PMP@Alb could be used as a useful tool to improve the efficacy of existing PDT by disrupting tumor vessel barriers through effective platelet inhibition.


Asunto(s)
Nanopartículas , Neoplasias/tratamiento farmacológico , Fotoquimioterapia , Albúminas/farmacología , Animales , Línea Celular Tumoral , Humanos , Masculino , Ratones Endogámicos C57BL , Fármacos Fotosensibilizantes/farmacología , Piperidinas/farmacología , Microambiente Tumoral
13.
Biol Res ; 54(1): 27, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34488902

RESUMEN

BACKGROUND: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. RESULTS: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. CONCLUSIONS: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.


Asunto(s)
Autofagia , Neoplasias de la Próstata , Apoptosis , Línea Celular Tumoral , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Especies Reactivas de Oxígeno , Triterpenos
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 501-506, 2021 Aug.
Artículo en Chino | MEDLINE | ID: mdl-34494518

RESUMEN

Objective To investigate the effects of osthole on the proliferation,apoptosis,and autophagy of human tongue cancer Tca8113 cells and explore its possible mechanism of action. Methods Tca8113 cells were cultured in vitro and divided into a control group without drugs and the experimental groups with 40,80,120,and 160 µmol/L osthole.The inhibitory effect of osthole on the proliferation of Tca8113 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay.Hoechst33342 staining method and annexin V-FITC/propidium iodide method were employed to detect the effect of osthole on the apoptosis of Tca8113 cells within 24 hours.Western blot was performed to detect the expression of apoptosis-related proteins(Bcl-2,Bax,and cleaved caspase-3)and autophagy-related proteins(LC3 and p62)in Tca8113 cells exposed to osthole. Results Osthole significantly inhibited the proliferation and induced the apoptosis of Tca8113 cells in a concentration-dependent manner,and it reduced the cell colony formation.Western blot results showed that osthole could up-regulate the expression of Bax and cleaved caspase-3 and down-regulate that of Bcl-2.At the same time,it increased the expression of LC3Ⅱ and P62 and reduced that of LC3Ⅰ. Conclusion Osthole may inhibit the proliferation of Tca8113 cells by promoting cell apoptosis and blocking autophagy flow to inhibit autophagy.


Asunto(s)
Neoplasias de la Lengua , Apoptosis , Autofagia , Línea Celular Tumoral , Proliferación Celular , Cumarinas , Humanos
15.
Mater Sci Eng C Mater Biol Appl ; 128: 112258, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34474818

RESUMEN

A novel polyelectrolyte nanocarrier was synthesized via layer-by-layer self-assembly of polycationic and polyanionic chains. The nanocarrier is composed of polyglutamate grafted chitosan core, dextran sulfate as a complexing agent, and polyethyleneimine shell decorated with folic acid. This polyelectrolyte complex has unique physicochemical properties so that the core is considered as an efficient carrier for LTX-315 and melittin peptides, and the shell is suitable for delivery of miR-34a. The spherical nanocarriers with an average size of 123 ± 5 nm and a zeta potential of -36 ± 1 mV demonstrated controlled-release of gene and peptides ensured a synergistic effect in establishing multiple cell death pathways on chemoresistance human breast adenocarcinoma cell line, MDA-MB-231. In vitro cell viability assays also revealed no cytotoxicity for the nanocarriers, and an IC50 of 15 µg/mL and 150 µg/mL for melittin and LTX-315, respectively, after 48 h, whereas co-delivery of melittin with miR-34a increased smart death induction by 54%.


Asunto(s)
Neoplasias de la Mama , Quitosano , MicroARNs/administración & dosificación , Nanopartículas , Neoplasias de la Mama/tratamiento farmacológico , Muerte Celular , Línea Celular Tumoral , Femenino , Humanos , Meliteno/farmacología , MicroARNs/genética , Oligopéptidos , Polielectrolitos
16.
Mater Sci Eng C Mater Biol Appl ; 128: 112305, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34474856

RESUMEN

In spite of established evidence of the synergistic combination of hydrophobic anticancer molecule and microRNA for breast cancer treatment, their in vivo delivery has not been realized owing to their instability in the biological milieu and varied physicochemical properties. The present work reports folate targeted hybrid lipo-polymeric nanoplexes for co-delivering DTX and miR-34a. These nanoplexes exhibited a mean size of 129.3 nm with complexation efficiency at an 8:1 N/P ratio. The obtained nanoplexes demonstrated higher entrapment efficiency of DTX (94.8%) with a sustained release profile up to 85% till 48 h. Further, an improved transfection efficiency in MDA-MB-231 and 4T1 breast cancer cells was observed with uptake primarily through lipid-raft and clathrin-mediated endocytosis. Further, nanoplexes showed improved cytotoxicity (~3.5-5 folds), apoptosis (~1.6-2.0 folds), and change in expression of apoptotic genes (~4-7 folds) compared to the free treatment group in breast cancer cells. In vivo systemic administration of FA-functionalized DTX and FAM-siRNA-loaded nanoplexes showed an improved area under the curve (AUC) as well as circulation half-life compared to free DTX and naked FAM-labelled siRNA. Acute toxicity studies of the cationic polymer showed no toxicity at a dose equivalent to 10 mg/kg based on the hematological, biochemical, and histopathological examination.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , MicroARNs/administración & dosificación , Nanopartículas , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Línea Celular Tumoral , Docetaxel/farmacología , Portadores de Fármacos/uso terapéutico , Femenino , Ácido Fólico , Humanos , MicroARNs/genética , Polímeros/uso terapéutico
17.
Anticancer Res ; 41(9): 4447-4453, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34475068

RESUMEN

BACKGROUND/AIM: The tumor microenvironment plays an important role in tumor progression. Tumor-associated macrophages (TAMs) have been reported to promote proliferation, invasion, metastasis, angiogenesis, and immunosuppression. Furthermore, angiogenesis has been reported to induce chemoresistance due to the inefficient distribution of drugs to cancer cells. However, the impact of TAMs on chemoresistance via angiogenesis in colorectal cancer (CRC) remains unclear. The aim of the study was to evaluate the impact of TAMs on the chemotherapeutic outcome in CRC. PATIENTS AND METHODS: We enrolled 54 patients who underwent chemotherapy for unresectable metastatic CRC after resection of the primary tumor. We evaluated the density of TAMs and the degree of angiogenesis by immunohistochemistry and then explored the correlation between the density of TAMs and chemotherapeutic outcome. Furthermore, we assessed any correlation between the density of TAMs and that of neovascularity. RESULTS: The high-TAMs group had a significantly worse progression-free survival (p=0.0006) and a poorer response rate (p=0.0274) than the low-TAMs group. In addition, a positive correlation was observed between the density of TAMs and the degree of neovascularity (r=0.665, p=0.0004). CONCLUSION: TAMs were shown to promote chemoresistance via angiogenesis in CRC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/irrigación sanguínea , Resistencia a Antineoplásicos , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/cirugía , Transición Epitelial-Mesenquimal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Microambiente Tumoral
18.
Anticancer Res ; 41(9): 4563-4570, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34475084

RESUMEN

BACKGROUND/AIM: Maspin has tumor-suppressor functions; however, its prognostic value in patients with oral squamous cell carcinoma (OSCC) remains unknown. We aimed to assess the prognostic importance of the subcellular localization of maspin in patients with OSCC. PATIENTS AND METHODS: Eighty resected specimens were analyzed by immunohistochemistry. Cytoplasmic-only expression observed in >10% of the tumor was defined as maspin-positive. RESULTS: The maspin-positive status (25%) was significantly associated with a higher recurrence rate and shorter disease-free survival (DFS). Cox's multivariate analysis showed that maspin-positive status was an independent factor for shorter DFS. All OSCC cell lines (HSC2, HSC3, HSC4, Ca9-22 and SAS) showed maspin protein localization to both the cytoplasm and nucleus using western blot analysis. In HSC4 cells, cell invasion was significantly increased in response to maspin knockdown. CONCLUSION: Cytoplasmic-only expression of maspin could be an independent poor prognostic factor for patients with OSCC.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Citoplasma/metabolismo , Neoplasias de la Boca/cirugía , Serpinas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Núcleo Celular/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Análisis Multivariante , Pronóstico , Análisis de Supervivencia
19.
Braz J Biol ; 83: e248746, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34495165

RESUMEN

Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.


Asunto(s)
Catequina , Neoplasias Colorrectales , Anexina A5 , Catequina/análogos & derivados , Catequina/farmacología , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Quercetina/farmacología
20.
Braz J Biol ; 83: e248708, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34468533

RESUMEN

Oral squamous cell carcinoma (OSCC) is a malignant tumour of Head and Neck Cancer (HNC). The recent therapeutic approaches used to treat cancer have adverse side effects. The natural agents exhibiting anticancer activities are generally considered to have a robust therapeutic potential. Curcuminoids, one of the major active compounds of the turmeric herb, are used as a therapeutic agent for several diseases including cancer. In this study, the cytotoxicity of curcuminoids was investigated against OSCC cell line HNO97. Our data showed that curcuminoids significantly inhibits the proliferation of HNO97 in a time and dose-dependent manner (IC50=35 µM). Cell cycle analysis demonstrated that curcuminoids increased the percentage of G2/M phase cell populations in the treated groups. Treating HNO97 cells with curcuminoids led to cell shrinking and increased detached cells, which are the typical appearance of apoptotic cells. Moreover, flow cytometry analysis revealed that curcuminoids significantly induced apoptosis in a time-dependent manner. Furthermore, as a response to curcuminoids treatment, comet tails were formed in cell nuclei due to the induction of DNA damage. Curcuminoids treatment reduced the colony formation capacity of HNO97 cells and induced morphological changes. Overall, these findings demonstrate that curcuminoids can in vitro inhibit HNC proliferation and metastasis and induce apoptosis.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Línea Celular Tumoral , Proliferación Celular , Diarilheptanoides , Humanos , Neoplasias de la Boca/tratamiento farmacológico
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