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1.
Int J Mol Sci ; 20(10)2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-31096713

RESUMEN

Classic Hodgkin lymphoma (cHL) is characterized by a few tumor cells surrounded by a protective, immunosuppressive tumor microenvironment composed of normal cells that are an active part of the disease. Hodgkin and Reed-Sternberg (HRS) cells evade the immune system through a variety of different mechanisms. They evade antitumor effector T cells and natural killer cells and promote T cell exhaustion. Using cytokines and extracellular vesicles, they recruit normal cells, induce their proliferation and "educate" (i.e. reprogram) them to become immunosuppressive and protumorigenic. Therefore, alternative treatment strategies are being developed to target not only tumor cells but also the tumor microenvironment. Here we summarize current knowledge on the ability of HRS cells to build their microenvironment and to educate normal cells to become immunosuppressive. We also describe therapeutic strategies to counteract formation of the tumor microenvironment and related processes leading to T cell exhaustion and repolarization of immunosuppressive tumor-associated macrophages.


Asunto(s)
Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/inmunología , Inmunosupresores/farmacología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Anticuerpos Monoclonales Humanizados/farmacología , Quimiocinas/metabolismo , Citocinas/metabolismo , Inmunosupresores/uso terapéutico , Células Asesinas Naturales , Maraviroc/farmacología , Nivolumab/farmacología , Pronóstico , Receptores CCR5/efectos de los fármacos , Células de Reed-Sternberg/efectos de los fármacos , Células de Reed-Sternberg/inmunología , Linfocitos T , Trabectedina/farmacología , Triptófano/análogos & derivados , Triptófano/farmacología , Escape del Tumor/efectos de los fármacos , Ácido Zoledrónico/farmacología
2.
Cancers (Basel) ; 11(4)2019 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-30987271

RESUMEN

We synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (C1-C8) and tested them in a panel of human cancer cell lines. We used osteosarcoma (MG-63), lung (A549), prostate (PC3 and DU145), breast (MCF-7), ovarian (A2780 and A2780cis, cisplatin- and doxorubicin-resistant), and cervical (ME-180 and R-ME-180, cisplatin resistant) cancer cell lines. We found that C2, C3, C6, and C7 were more cytotoxic than cisplatin in all cell lines tested and overcame cisplatin and doxorubicin resistance in A2780cis and R-ME-180 cells. In the PC3 prostate cancer cell line, the gold (III) complex C6 ([Au2(BPM)(DMDTC)2]Cl4) induced apoptosis and double-stranded DNA breaks, modified cell cycle phases, increased Reactive Oxigen Species (ROS) generation, and reduced thioredoxin reductase and proteasome activities. It inhibited PC3 cell migration and was more cytotoxic against PC3 cells than normal human adipose-derived stromal cells. In mice bearing PC3 tumor xenografts, C6 reduced tumor growth by more than 70% without causing weight loss. Altogether, our results demonstrate the anticancer activity of these new gold (III) complexes and support the potential of C6 as a new agent for prostate cancer treatment.

3.
Haematologica ; 104(3): 564-575, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30309853

RESUMEN

Classic Hodgkin lymphoma tumor cells express a functional CCR5 receptor, and tumor tissues express high CCL5 levels, suggesting that CCL5-CCR5 signaling is involved in tumor-microenvironment formation and tumor growth. Using the CCR5 antagonist, maraviroc, and a neutralizing anti-CCL5 antibody, we found that CCL5 secreted by classic Hodgkin lymphoma cells recruited mesenchymal stromal cells and monocytes. The "education" of mesenchymal stromal cells by tumor cell-conditioned medium enhanced mesenchymal stromal cells' proliferation and CCL5 secretion. In turn, educated mesenchymal stromal cell-conditioned medium increased the clonogenic growth of tumor cells and monocyte migration, but these effects were reduced by maraviroc. Monocyte education by tumor cell-conditioned medium induced their growth and reprogrammed them towards immunosuppressive tumor-associated macrophages that expressed IDO and PD-L1 and secreted IL-10, CCL17 and TGF-ß. Educated monocyte-conditioned medium slowed the growth of phytohemagglutinin-activated lymphocytes. Maraviroc decreased tumor cell growth and synergized with doxorubicin and brentuximab vedotin. A three-dimensional heterospheroid assay showed that maraviroc counteracted both the formation and viability of heterospheroids generated by co-cultivation of tumor cells with mesenchymal stromal cells and monocytes. In mice bearing tumor cell xenografts, maraviroc reduced tumor growth by more than 50% and inhibited monocyte accumulation, without weight loss. Finally, in classic Hodgkin lymphoma human tumor tissues, CCL5 and CD68 expression correlated positively, and patients with high CCL5 levels had poor prognosis. In conclusion, since the present challenges are to find molecules counteracting the formation of the immunosuppressive tumor microenvironment or new, less toxic drug combinations, the repurposed drug maraviroc may represent a new opportunity for classic Hodgkin lym phoma treatment.

4.
Int J Mol Sci ; 19(5)2018 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-29772686

RESUMEN

Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects. C-C chemokine ligand 5 (CCL5) is a chemotactic cytokine, and its expression and secretion are regulated in T cells. C-C chemokine receptor type 5 (CCR5) is expressed in T cells, macrophages, other leukocytes, and certain types of cancer cells. The interaction between CCL5 and CCR5 plays an active role in recruiting leukocytes into target sites. This review summarizes recent information on the role of the CCL5 chemokine and its receptor CCR5 in GC cell proliferation, metastasis formation, and in the building of an immunosuppressive TME. Moreover, it highlights the development of new therapeutic strategies to inhibit the CCL5/CCR5 axis in different ways and their possible clinical relevance in the treatment of GC.


Asunto(s)
Quimiocina CCL5/metabolismo , Receptores CCR5/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Animales , Antagonistas de los Receptores CCR5/farmacología , Antagonistas de los Receptores CCR5/uso terapéutico , Transformación Celular Neoplásica/metabolismo , Progresión de la Enfermedad , Humanos , Terapia Molecular Dirigida , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos
5.
Oncotarget ; 8(26): 42926-42938, 2017 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-28477013

RESUMEN

Zoledronic Acid (ZA) rapidly concentrates into the bone and reduces skeletal-related events and pain in bone metastatic prostate cancer (PCa), but exerts only a limited or absent impact as anti-cancer activity. Recently, we developed self-assembling nanoparticles (NPS) encapsulating zoledronic acid (NZ) that allowed a higher intratumor delivery of the drug compared with free zoledronic acid (ZA) in in vivo cancer models of PCa. Increasing evidence suggests that Bone Marrow (BM) Mesenchymal stromal cells (BM-MSCs) are recruited into the stroma of developing tumors where they contribute to progression by enhancing tumor growth and metastasis.We demonstrated that treatment with NZ decreased migration and differentiation into adipocytes and osteoblasts of MSCs and inhibited osteoclastogenesis. Treatment with NZ reduced the capability of MSCs to promote the migration and the clonogenic growth of the prostate cancer cell lines PC3 and DU145. The levels of Interleukin-6 and of the pro-angiogenic factors VEGF and FGF-2 were significantly reduced in MSC-CM derived from MSCs treated with NZ, and CCL5 secretion was almost totally abolished. Moreover, treatment of MSCs with supernatants from PC3 cells, leading to tumor-educated MSCs (TE-MSCs), increased the secretion of IL-6, CCL5, VEGF and FGF-2 by MSCs and increased their capability to increase PC3 cells clonogenic growth. Treatment with NZ decreased cytokine secretion and the pro-tumorigenic effects also of TE-MSCS. In conclusion, demonstrating that NZ is capable to inhibit the cross talk between MSCs and PCa, this study provides a novel insight to explain the powerful anticancer activity of NZ on PCa.


Asunto(s)
Inductores de la Angiogénesis/metabolismo , Comunicación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Humanos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Nanopartículas , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Microambiente Tumoral/efectos de los fármacos , Ácido Zoledrónico
6.
Oncotarget ; 8(1): 490-505, 2017 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-27888799

RESUMEN

We synthesized, characterized and tested in a panel of cancer cell lines, nine new bipyridine gold(III) dithiocarbamate-containing complexes. In vitro studies demonstrated that compounds 1, 2, 4, 5, 7 and 8 were the most cytotoxic in prostate, breast, ovarian cancer cell lines and in Hodgkin lymphoma cells with IC50 values lower than the reference drug cisplatin. The most active compound 1 was more active than cisplatin in ovarian (A2780cis and 2780CP-16) and breast cancer cisplatin-resistant cells. Compound 1 determined an alteration of the cellular redox homeostasis leading to increased ROS levels, a decrease in the mitochondrial membrane potential, cytochrome-c release from the mitochondria and activation of caspases 9 and 3. The ROS scavenger NAC suppressed ROS generation and rescued cells from damage. Compound 1 resulted more active in tumor cells than in normal human Mesenchymal stromal cells. Gold compounds were active independent of p53 status: exerted cytotoxic effects on a panel of non-small cell lung cancer cell lines with different p53 status and in the ovarian A2780 model where the p53 was knocked out. In conclusion, these promising results strongly indicate the need for further preclinical evaluation to test the clinical potential of these new gold(III) complexes.


Asunto(s)
Antineoplásicos/farmacología , Cisplatino/farmacología , Neoplasias/tratamiento farmacológico , Compuestos Orgánicos de Oro/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Acetilcisteína/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Sistemas CRISPR-Cas/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos , Depuradores de Radicales Libres/farmacología , Técnicas de Silenciamiento del Gen/métodos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Neoplasias/patología , Compuestos Orgánicos de Oro/química , Compuestos Orgánicos de Oro/uso terapéutico , Piridinas/química , Especies Reactivas de Oxígeno/metabolismo , Tiocarbamatos/química , Proteína p53 Supresora de Tumor/genética
7.
Cancer Lett ; 380(1): 243-52, 2016 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-26474544

RESUMEN

Classical Hodgkin lymphoma (cHL) is characterized by few tumor cells surrounded by immune cells, fibroblasts, specialized mesenchymal stromal cells and endothelial cells, representing together with their products an active part of the disease. Hodgkin and Reed-Sternberg (HRS) cells can secrete cytokines/chemokines and angiogenic factors capable of recruiting and/or inducing the proliferation of the surrounding cells and can also interact with distant sites of the microenvironment by secreting exosomes. To escape from a useful anti-tumor response due to the recognition by T and NK cells, HRS cells down-regulate HLA molecules, produce immune suppressive cytokines that inhibit cytotoxic responses, and induce an immunosuppressive phenotype on T lymphocytes and Monocytes. HRS cells survive, proliferate and are protected from the cytotoxic effects of chemotherapy agents by soluble factors or by the direct contact with inflammatory and stromal cells of the tumor microenvironment (TME). A summary of the current knowledge about classical Hodgkin Lymphoma focusing on the cross-talk between tumor cells and the microenvironment leading to immune-escape, angiogenesis tumor growth/survival and drug resistance will be reviewed here.


Asunto(s)
Antineoplásicos/uso terapéutico , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Enfermedad de Hodgkin/tratamiento farmacológico , Escape del Tumor , Microambiente Tumoral , Proteínas Angiogénicas/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Comunicación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Humanos , Neovascularización Patológica , Transducción de Señal/efectos de los fármacos
9.
Clin Cancer Res ; 20(21): 5496-506, 2014 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-25231401

RESUMEN

PURPOSE: Cisplatin and its platinum derivatives are first-line chemotherapeutic agents in the treatment of ovarian cancer; however, treatment is associated with tumor resistance and significant toxicity. Here we investigated the antitumoral activity of lipoplatin, one of the most promising liposomal platinum drug formulations under clinical investigation. EXPERIMENTAL DESIGN: In vitro effects of lipoplatin were tested on a panel of ovarian cancer cell lines, sensitive and resistant to cisplatin, using both two-dimensional (2D) and 3D cell models. We evaluated in vivo the lipoplatin anticancer activity using tumor xenografts. RESULTS: Lipoplatin exhibited a potent antitumoral activity in all ovarian cancer cell lines tested, induced apoptosis, and activated caspase-9, -8, and -3, downregulating Bcl-2 and upregulating Bax. Lipoplatin inhibited thioredoxin reductase enzymatic activity and increased reactive oxygen species accumulation and reduced EGF receptor (EGFR) expression and inhibited cell invasion. Lipoplatin demonstrated a synergistic effect when used in combination with doxorubicin, widely used in relapsed ovarian cancer treatment, and with the albumin-bound paclitaxel, Abraxane. Lipoplatin decreased both ALDH and CD133 expression, markers of ovarian cancer stem cells. Multicellular aggregates/spheroids are present in ascites of patients and most contribute to the spreading to secondary sites. Lipoplatin decreased spheroids growth, vitality, and cell migration out of preformed spheroids. Finally, lipoplatin inhibited more than 90% tumor xenograft growth with minimal systemic toxicity, and after the treatment suspension, no tumor progression was observed. CONCLUSION: These preclinical data suggest that lipoplatin has potential for clinical assessment in aggressive cisplatin-resistant patients with ovarian cancer.


Asunto(s)
Cisplatino/farmacología , Liposomas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Antígeno AC133 , Paclitaxel Unido a Albúmina , Albúminas/farmacología , Antígenos CD/genética , Antígenos CD/metabolismo , Antineoplásicos/farmacología , Caspasas/genética , Caspasas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Invasividad Neoplásica/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Paclitaxel/farmacología , Péptidos/genética , Péptidos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
10.
Future Med Chem ; 6(11): 1249-63, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25162999

RESUMEN

BACKGROUND: Recently, novel gold(III)-dithiocarbamato peptidomimetics, designed to target peptide transporters upregulated in several tumor cells have shown promise as anticancer agents. RESULTS: The biological behavior of the most promising derivatives AuD8 and AuD9 was studied in PC3 and DU145 prostate cancer cells. They exert higher cytotoxicity in vitro than the reference drug cisplatin and induce apoptosis, promoting mitochondrial membrane permeabilization and stimulating reactive oxygen species generation. Moreover, they inhibit both selenoenzyme thioredoxin reductase and proteasome activity. Additionally, AuD8 effectively reduces tumor growth in prostate tumor-bearing nude mice with minimal systemic toxicity. CONCLUSION: Altogether, our results provide insights into the anticancer activity of these gold(III)-dithiocarbamato peptidomimetics and support their potential as new agents for prostate cancer treatment.


Asunto(s)
Compuestos de Oro/farmacología , Peptidomiméticos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Tiocarbamatos/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasas/fisiología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Ratones , Mitocondrias/efectos de los fármacos , Trasplante de Neoplasias , Especies Reactivas de Oxígeno , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Cancer Lett ; 349(1): 26-34, 2014 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-24704296

RESUMEN

The NF-κB inhibitor DHMEQ has shown preclinical activity in classical Hodgkin Lymphoma (cHL). Here we evaluated if DHMEQ could affect microenvironmental interactions and formation and improve the activity of drugs used in relapsed/refractory cHL. We demonstrated that DHMEQ down-regulated the NF-κB target genes IRF4 and CD40, the secretion of IL-6, CCL5, CCL17 and generated ROS. Cytotoxicity, CD30 down-modulation and CD30 shedding by DHMEQ were prevented by ROS scavenger NAC. DHMEQ overcame stimuli from CD40 engagement and fibroblasts and enhanced doxorubicin, cisplatin and gemcitabine activity. Our results suggest that DHMEQ may be a promising agent for future therapeutic strategies in cHL.


Asunto(s)
Antineoplásicos/farmacología , Benzamidas/farmacología , Ciclohexanonas/farmacología , Enfermedad de Hodgkin/tratamiento farmacológico , FN-kappa B/antagonistas & inhibidores , Microambiente Tumoral/efectos de los fármacos , Antígenos CD40/metabolismo , Línea Celular Tumoral , Quimiocina CCL17/metabolismo , Quimiocina CCL5/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Sinergismo Farmacológico , Enfermedad de Hodgkin/metabolismo , Humanos , Factores Reguladores del Interferón/metabolismo , Interleucina-6/metabolismo , Antígeno Ki-1/metabolismo , Especies Reactivas de Oxígeno/metabolismo
12.
Leuk Lymphoma ; 55(1): 149-59, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23647062

RESUMEN

Bortezomib is a proteasome inhibitor active in classical Hodgkin lymphoma (cHL) cell lines, but poorly active in the clinic when used as a single agent, suggesting that the microenvironment could protect from drug efficacy. Therefore, we investigated the effects of bortezomib activity in the presence of HL-associated fibroblasts (HL-AFs) and sCD40L. We found that co-cultivation with human HL-AFs or the addition of sCD40L during bortezomib treatment protected cHL cells from apoptosis and cytotoxicity and rescued the down-regulation of the survival factor interferon regulatory factor 4 (IRF4). In contrast, bortezomib treatment before co-cultivation with HL-AFs inhibited in a dose-dependent manner cHL cell adhesion to HL-AFs and completely overcame HL-AF protection against drug activity. Consistently, we found that bortezomib treatment down-regulated the surface expression of CD49d and CD44, which mediate the adhesion of cHL cells to HL-AFs, and of CD54 and CD40, which mediate the adhesion to CD40L+ rosetting T-cells. These preclinical findings suggest that the low in vivo activity of bortezomib as a single agent may be due to a protective influence of the microenvironment. However, inclusion of bortezomib in the cHL drug regimen, by reducing IRF4 expression and interactions with the microenvironment, could increase the efficacy of current chemotherapeutic treatment of relapsed/refractory cHL.


Asunto(s)
Ácidos Borónicos/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Factores Reguladores del Interferón/metabolismo , Pirazinas/farmacología , Bortezomib , Ligando de CD40/metabolismo , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo , Activación Enzimática/efectos de los fármacos , Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Enfermedad de Hodgkin/genética , Humanos , Factores Reguladores del Interferón/genética , FN-kappa B/metabolismo
13.
Gynecol Oncol ; 131(3): 744-52, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24029417

RESUMEN

OBJECTIVE: Cisplatin-based chemotherapy has been shown to improve survival in cervical cancer; however, treatment is associated with tumor resistance and significant toxicity. Lipoplatin is a new liposomal formulation of cisplatin, developed to reduce cisplatin toxicity, to improve drug accumulation at tumor sites and to overcome drug resistance. The aim of this study is to analyze the antitumoral activity of lipoplatin against cisplatin-resistant cervical cancer cells and to investigate its mechanism of action. METHODS: The activity and mechanism of action of lipoplatin were studied in the ME-180 cervical cancer cell line and its cisplatin-resistant clone R-ME-180 and HeLa cells using cell proliferation assays, flow cytometry, ELISA assay, cell migration, spheroids and tumor xenograft. RESULTS: We demonstrated that lipoplatin exhibited a potent antitumoral activity on HeLa, ME-180 cells and its cisplatin-resistant clone R-ME-180. Lipoplatin inhibited cell proliferation in a dose-dependent manner and was more active than the reference drug cisplatin in R-ME-180 cells and induced apoptosis, as evaluated by Annexin-V staining and DNA fragmentation, caspases 9 and 3 activation, Bcl-2, and Bcl-xL down-regulation, but Bax up-regulation inhibited thioredoxin reductase (TrxR) enzymatic activity and increased reactive oxygen species (ROS) accumulation; reduced EGFR expression and inhibited both migration and invasion. R-ME-180, but not ME-180 cells, generated three-dimensional (3D)-multicellular spheroids expressing the cancer stem cell marker ALDH. The ability of R-ME-180 cells to form spheroids in vitro and tumors in nude mice was also remarkably decreased by lipoplatin. CONCLUSIONS: Overall, our results suggest that lipoplatin has potential for the treatment of cisplatin-resistant cervical cancer.


Asunto(s)
Cisplatino/administración & dosificación , Liposomas/administración & dosificación , Neoplasias del Cuello Uterino/tratamiento farmacológico , Aldehído Deshidrogenasa/metabolismo , Animales , Apoptosis/efectos de los fármacos , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Cisplatino/farmacología , Resistencia a Antineoplásicos , Receptores ErbB/biosíntesis , Femenino , Células HeLa , Humanos , Ratones , Ratones Desnudos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Especies Reactivas de Oxígeno/metabolismo , Esferoides Celulares , Reductasa de Tiorredoxina-Disulfuro/antagonistas & inhibidores , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Ensayos Antitumor por Modelo de Xenoinjerto
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