RESUMO
Recent progress in cuproptosis sheds light on the development of treatment approaches for advancing sonodynamic therapy (SDT) due to its unique cell death mechanism. Herein, we elaborately developed an intelligent cell-derived nanorobot (SonoCu), composed of macrophage-membrane-camouflaged nanocarrier encapsulating copper-doped zeolitic imidazolate framework-8 (ZIF-8), perfluorocarbon, and sonosensitizer Ce6, for synergistically triggering cuproptosis-augmented SDT. SonoCu not only improved tumor accumulation and cancer-cell uptake through cell-membrane camouflaging but responded to ultrasound stimuli to enhance intratumor blood flow and oxygen supply, which consequently overcame treatment barriers and activated sonodynamic cuproptosis. Importantly, the SDT effectiveness could be further amplified by cuproptosis through multiple mechanisms, including reactive oxygen species accumulation, proteotoxic stress, and metabolic regulation, which synergistically sensitized cancer cell death. Particularly, SonoCu exhibited ultrasound-responsive cytotoxicity against cancer cells but not healthy cells, endowing it with good biosafety. Therefore, we present the first anticancer combination of SDT and cuproptosis, which may inspire studies pursuing a rational multimodal treatment strategy.
Assuntos
Apoptose , Neoplasias , Terapia por Ultrassom , Humanos , Morte Celular , Neoplasias/terapia , Espécies Reativas de Oxigênio/metabolismo , Ultrassonografia , CobreRESUMO
Hepatocellular carcinoma (HCC) is one of the most common primary malignancies. Drug resistance has significantly prevented the clinical application of sorafenib (SF), a first-line targeted medicine for the treatment of HCC. Solamargine (SM), a natural alkaloid, has shown potential antitumor activity, but studies about antitumor effect of SM are obviously insufficient in HCC. In the present study, we found that SM significantly inhibited the growth of HCC and enhanced the anticancer effect of SF. In brief, SM significantly inhibited the growth of HepG2 and Huh-7 cells. The combination of SM and SF showed a synergistic antitumor effect. Mechanistically, SM downregulated the expression of long noncoding RNA HOTTIP and TUG1, followed by increasing the expression of miR-4726-5p. Moreover, miR-4726-5p directly bound to the 3'-UTR region of MUC1 and decreased the expression of MUC1 protein. Overexpression of MUC1 partially reversed the inhibitory effect of SM on HepG2 and Huh-7 cells viability, which suggested that MUC1 may be the key target in SM-induced growth inhibition of HCC. More importantly, the combination of SM and SF synergistically restrained the expression of MUC1 protein. Taken together, our study revealed that SM inhibited the growth of HCC and enhanced the anticancer effect of SF through HOTTIP-TUG1/miR-4726-5p/MUC1 signaling pathway. These findings will provide potential therapeutic targets and strategies for the treatment of HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Mucina-1/genética , Mucina-1/metabolismo , Mucina-1/uso terapêutico , RNA Longo não Codificante/genética , Alcaloides de Solanáceas , Sorafenibe/farmacologiaRESUMO
Combination therapy with conventional chemotherapeutic drugs strongly demonstrates a good approach to reduce cytotoxicity, resistance, and the dose of the potent anticancer drugs. The purpose of this research was to design and characterize liposome incorporating celecoxib (CEL) and doxorubicin hydrochloride (DOX) and investigate the anti-tumor efficacy of this combination on different tumor cells. A simple comparison study had been performed for liposomes formulation using thin-film hydration method and pH-gradient method. HSPC-incorporated liposomes were chosen for encapsulation of both CEL and DOX. The formulations showed small particle size and polydispersity index with high encapsulation efficiency. DOX/CEL liposomes displayed the strongest cytotoxicity against B16 and MGC80-3 cells in comparison to the corresponding drug solutions. By incorporation of both agents, a significant reduction in IC50 from 0.927 to 0.198 µg/ml and from 0.81 to 0.535 µg/ml against B16 cells and MGC80-3 cells, respectively, was observed. CEL also significantly improved the intracellular retention and accumulation of DOX in vitro. Our data suggest that the developed liposomal formulation proved to be the most effective formulative strategy as a dual drug delivery system for incorporation of both doxorubicin HCL and CEL and could be considered a useful tool for enhancing the therapeutic efficacy of the anticancer drug.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Celecoxib/administração & dosagem , Celecoxib/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Animais , Antineoplásicos/química , Celecoxib/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipossomos , Camundongos , Tamanho da Partícula , Relação Estrutura-Atividade , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
Interventional therapies are increasingly used in clinical trials for hepatocellular carcinoma (HCC). Sorafenib is the front-line remedy for HCC, however, chemoresistance occurs immutably and affects the effectiveness of treatment. In a previous study, a norcantharidin liposome emulsion hybrid (NLEH) delivery system for HCC was developed. This study aims to examine the therapeutic effects of the combination of intratumoral injection of NLEH and sorafenib in treating HCC. Sorafenib combined with NLEH activated the apoptosis pathway by synergistically upregulating caspase-9, promoting cytotoxicity, apoptosis (64.57%), and G2/M cell cycle arrest (48.96%). Norcantharidin could alleviate sorafenib resistance by counteracting sorafenib-induced phosphorylation of Akt. Additionally, intratumoral injection of NLEH exhibited a sustained accumulation in the tumor within 24 h and didn't distribute to other major organs. Intratumoral injection of NLEH in combination with oral sorafenib displayed the most potent tumor growth inhibitory effect (77.91%) in vivo. H&E staining results and the indicators of the renal and liver function tests demonstrated the safety of this combination therapy. Overall, these results showed that intratumoral injection of NLEH in combination with oral sorafenib treatment represented a rational potential therapeutic option for HCC.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Lipossomos/farmacologia , Neoplasias Hepáticas/patologia , Emulsões/farmacologia , Injeções Intralesionais , Linhagem Celular Tumoral , Apoptose , Proliferação de CélulasRESUMO
Amlodipine is a Ca2+ channel blocker commonly used to cardiovascular diseases such as hypertension and angina; however, its anticancer effects in lung cancer A549 cells remain unknown. In the present study, we explored the antitumor effects and molecular mechanisms underlying the action of amlodipine in non-small cell lung cancer (NSCLC) A549 cells in vitro and in vivo. We observed that amlodipine suppressed the proliferation of A549 lung cancer cells by arresting the tumor cell cycle. Mechanistically, our results revealed that amlodipine could attenuate the phosphoinositide 3 kinase (PI3K)/Akt and Raf/MEK/extracellular signal-regulated kinase (ERK) pathways through epidermal growth factor receptor (EGFR) and modulated cell cycle-related proteins such as cyclin D1, p-Rb, p27, and p21. Subsequently, amlodipine combined with gefitinib could synergistically inhibit cell proliferation by arresting the cell cycle. Moreover, amlodipine combined with gefitinib effectively attenuated the growth of A549 lung cancer xenografts when compared with monotherapy, affording an excellent therapeutic effect. Collectively, our results indicate that amlodipine alone or combined with the novel anticancer drug gefitinib might be a potential therapeutic strategy for NSCLC patients with wild-type EGFR.
RESUMO
A novel kind of anti-cancer pharmacosome (named NPC-D) derived from Doxifluridine (5'-DFUR) was described, which could be activated by tumor microenvironments (TMEs). The NPC-D with H2O2-sensitive linker was dispersed well in water and simultaneously interacted with nucleic acids including plasmids encoding miR-122 (p122) and EpCAM-targeted aptamer (ap1) via charge interaction and hydrogen bonding. The integrated nanosystem (p122-ap1@NPC-D) was found to unleash by programmed TMEs (high level of H2O2 and low pH) to efficiently transfect miR-122 into MHCC-LM3 cells, followed by the releases of 5-FU. Besides, p122-ap1@NPC-D significantly countered the chemotherapy resistance and played a synergistic effect. These unique nanoparticles dramatically enhanced the anti-proliferation, and modulated the cellular apoptosis by the down-regulation of various signal pathways which imparted a bright application prospect in HCC treatment.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Floxuridina , Regulação Neoplásica da Expressão Gênica , Humanos , Peróxido de Hidrogênio , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , MicroRNAs/genética , Microambiente TumoralRESUMO
The topical delivery of chemotherapeutics is a promising approach for the management of skin disorders. However, diverse pharmaceutical strategies are essential to allow penetration of large quantities of drugs to tumor tissue. Herein, an attempt was made to investigate the use of Derma roller® microneedles in combination with doxorubicin HCl (DOX) and celecoxib (CEL) co-loaded liposomes as a potential therapeutic approach for the management of melanoma. DOX/CEL co-loaded liposomes/Gels were prepared and characterized. The results showed that microneedle pretreatment with liposomes gel increased DOX penetration into the skin approximately 2-fold compared with the passive delivery. Both CEL liposomes and DOX liposomes caused significant growth inhibition on B16 cells. Besides, DOX/CEL co-loaded liposome was found more cytotoxic than DOX/CEL solution and single drug loaded liposome. The transdermal delivery of DOX/CEL co-loaded liposome successfully inhibited subcutaneous melanoma in female BALB/nude mice, and the co-administration of DOX/CEL with liposomes was better and significantly enhanced the antitumor effect more than single-drug-loaded liposomes. Furthermore, Dermarollers treatment prior to gel application strongly improved the tumor inhibition rate. DOX/CEL co-loaded liposome delivery via microneedles is a promising strategy for skin tumor treatment with targeting inhibition efficiency and negligible side effects.
Assuntos
Antineoplásicos/administração & dosagem , Celecoxib/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Agulhas , Administração Cutânea , Animais , Antineoplásicos/farmacologia , Celecoxib/farmacologia , Morte Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Géis , Lipossomos , Melanoma Experimental/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Absorção Cutânea/efeitos dos fármacos , Eletricidade Estática , Carga Tumoral/efeitos dos fármacosRESUMO
In this work, we have successfully designed and formulated a doxorubicin-loaded polypeptide-based multilayer assembled gold nanorod (DH-GNR). We have hypothesized that near-infrared (NIR) laser irradiation of DH-GNR will combine the benefits of chemotherapy and photothermal therapy. The GNR was surface functionalized with poly-glutamic acid (PGA) and poly-l-Lysine (PLL) with a final layer of hyaluronic acid (HA) that could also serve as a targeting ligand toward the overexpressed CD44 receptors in ovarian cancer cells. The zigzag ζ potential of nanoparticle is a proof of successful assembly of alternative polymers on the GNR surface. NIR irradiation exhibited a burst release of drug in pH 7.4 and pH 5.0 buffer conditions. The combination of doxorubicin (DOX)-based chemotherapy and GNR-based photothermal therapy exhibited a synergistic effect in killing the SKOV3 cancer cells. DH-GNR(+NIR) induced a 82.5% apoptosis (combined early and late apoptosis) compared with only 35.2 and 38.5% for DOX or DH-GNR(-NIR) treated cell group. Results clearly suggest that the excessive reactive oxygen species (ROS) generation in DH-GNR (+NIR) might be responsible for the cell apoptosis and cell death. The promising anticancer effect of DH-GNR will be of great potential in the treatment of ovarian cancers and worth further development for treating other malignant tumors.
Assuntos
Materiais Revestidos Biocompatíveis , Doxorrubicina , Ouro , Nanopartículas Metálicas , Nanotubos/química , Neoplasias Ovarianas/tratamento farmacológico , Fotoquimioterapia , Ácido Poliglutâmico , Polilisina , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Ouro/química , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ácido Poliglutâmico/química , Ácido Poliglutâmico/farmacologia , Polilisina/química , Polilisina/farmacologiaRESUMO
In this study, we investigated the synergistic effect of L-buthionine sulfoximine (BSO) on the chlorin e6 (Ce6)-based photodynamic therapy (PDT) of cancer cells. Among various cancer cells, HCT116 cells have highest intracellular L-glutathione (GSH) level and SNU478 cells showed the lowest GSH level. BSO alone showed negligible intrinsic cytotoxicity against CCD986sk cells. Since HCT116 and SNU478 cells showed the highest and the lowest intracellular GSH levels, respectively, those were used to test synergistic effect on the Ce6-based PDT. In the absence of light, BSO and Ce6 combination did not practically increase reactive oxygen species (ROS) in either of HCT116 or SNU478 cells, while light irradiation increased ROS level dose-dependently. 10 µM BSO treatment significantly depleted total GSH level in cancer cells, i.e. total GSH level decreased to one-fourth of the control in HCT116 cells while it decreased to two-fifth of the control treatment at SNU478 cell. BSO showed synergistic effect on the ROS production in HCT116 cells while it has practically no benefits in ROS production of SNU478 cells. No synergistic effect was observed in viability of SNU478 cells because BSO itself was cytotoxic to SNU478 cells. However, BSO had negligible cytotoxicity against HCT116 cells and showed synergistic anticancer effect in combination with Ce6-based PDT. Furthermore, the addition of glutathione reduced ethyl ester (GSH-OEt), recovered intracellular GSH level, and cell viability with reduced the intracellular ROS level. We suggest that synergistic effect of BSO in the Ce6-based PDT should be considered with intrinsic intracellular GSH level of cancer cells.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Butionina Sulfoximina/farmacologia , Fotoquimioterapia/métodos , Porfirinas/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Butionina Sulfoximina/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Clorofilídeos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Glutationa/metabolismo , Células HCT116 , Humanos , Camundongos , Porfirinas/uso terapêutico , Espécies Reativas de OxigênioRESUMO
Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro, combination treatment requires improvement in vivo due to uncontrolled ratiometric delivery. In this study, a tumor-targeting lipodisk nanoparticle formulation was developed for ratiometric loading and the transportation of two hydrophobic model drugs, doxorubicin (DOX) and paclitaxel (PTX), in one single platform. Furthermore, a slightly acidic pH-sensitive peptide (SAPSP) incorporated into lipodisks effectively enhanced the tumor-targeting and cell internalization. The obtained co-loaded lipodisks were approximately 30â¯nm with a pH-sensitive property. The ratiometric co-delivery of two drugs via lipodisks was confirmed in both the drug-resistant MCF-7/ADR cell line and its parental MCF-7 cell line in vitro, as well as in a tumor-bearing mouse model in vivo compared with a cocktail solution of free drugs. Co-loaded lipodisks exerted improved cytotoxicity to tumor cells in culture, particularly to drug-resistant tumor cells at synergistic drug ratios. In an in vivo xenograft mouse model, the anti-tumor ability of co-loaded lipodisks was evidenced by the remarkable inhibitory effect on tumor growth of either MCF-7 or MCF-7/ADR tumors, which may be attributed to the increased and ratiometric accumulation of both drugs in the tumor tissues. Therefore, tumor-specific lipodisks were crucial for the combination treatment of DOX and PTX to completely exert a synergistic anti-cancer effect. It is concluded that for co-loaded lipodisks, cytotoxicity data in vitro could be used to predict their inhibitory activity in vivo, potentially enhancing the clinical outcome of synergistic therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanopartículas , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Doxorrubicina/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Células MCF-7 , Camundongos , Camundongos Nus , Paclitaxel/administração & dosagem , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Curcumin is an anticancer compound that exerts anti-proliferative and apoptotic effects via multiple molecular targets. The purpose of the present study was to investigate the anticancer effects of curcumin in combination with 5-fluorouracil plus cisplatin (FP) on the MGC-803 human gastric cancer cell line. Following treatment with curcumin and/or FP for 24, 48 and 72 h, cell viability, cell cycle progression and the apoptosis rate were evaluated using an MTT assay, flow cytometry and dual acridine orange/ethidium bromide staining, respectively. In addition, colony formation, Transwell migration and caspase-3/caspase-8 activity assays were performed. The expression of the apoptosis regulator B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected by western blotting analysis. Following treatment with curcumin and/or FP, cell viability, colony formation and cell migration were significantly reduced compared with the untreated control group. The rate of apoptosis, caspase-3/caspase-8 activity and the expression of Bax were significantly increased, whereas Bcl-2 expression was significantly reduced following treatment with curcumin and/or FP, compared with the untreated control group. The efficacy of curcumin combined with low-dose FP was significantly increased, compared with that of curcumin combined with high-dose FP (P<0.05). Therefore, curcumin may enhance the anticancer effects of FP chemotherapy in MGC-803 cells through the promotion of apoptosis via the caspase-3/caspase-8, Bcl-2 and Bax signaling pathways. These results suggest that curcumin may serve as a synergistic drug with chemotherapy regimen FP for the treatment of gastric cancer.
RESUMO
Recently, the global trend in the field of nanomedicine has been toward the design of highly sophisticated drug delivery systems with specific targeting and synergistic therapeutic functions for improving therapeutic efficacy. But offering sophistication generally increases their complexity that might be disadvantageous in pharmaceutical development. We hypothesize that using a macromolecular prodrug with a dual role will be conductive to integrating its dual function into self-targeted multidrug co-delivery and combination cancer therapy. In this paper, the on-off switching function-responsive, macromolecular methotrexate (MTX) prodrug-self-targeted, controlled-/sustained-release, and high drug-loading hydroxylcamptothecin (HCPT) drug nanospheres were prepared and characterized. The self-targeting system can co-deliver multi-drug to different action sites with distinct anticancer mechanisms to specifically target folate receptors-overexpressing cancer cells with synergistic therapeutic efficiency.
Assuntos
Camptotecina/administração & dosagem , Camptotecina/farmacologia , Portadores de Fármacos/administração & dosagem , Metotrexato/administração & dosagem , Metotrexato/farmacologia , Nanosferas/administração & dosagem , Nanosferas/química , Animais , Camptotecina/química , Camptotecina/farmacocinética , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Concentração Inibidora 50 , Metotrexato/química , Metotrexato/farmacocinética , Camundongos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Regulation of gene expression using p53 is a promising strategy for treatment of numerous cancers, and chemotherapeutic drug dichloroacetate (DCA) induces apoptosis and growth inhibition in tumor, without apparent toxicity in normal tissues. Combining DCA and p53 gene could be an effective way to treat tumors. The progress towards broad applications of DCA/p53 combination requires the development of safe and efficient vectors that target to specific cells. In this study, we developed a DSPE-PEG-AA (1,2-distearoryl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol-2000)] ammonium salt-anisamide) modified reconstituted high-density lipoprotein-based DCA/p53-loaded nanoparticles (DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes), which was fabricated as a drug/gene dual-targeting co-delivery system for potential cancer therapy. Here, DCA-PEI was utilized to effectively condense the p53 plasmid, to incorporate the plasmid into rHDL and to act as an antitumor drug to inhibit tumor cell growth. The DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes exhibited desirable and homogenous particle size, neutral surface charge and low cytotoxicity for normal cells in vitro. The results of confocal laser scanning microscopy (CLSM) and flow cytometry confirmed that the scavenger receptor class B type I (SR-BI) and sigma receptor mediated dual-targeting function of the complexes inducing efficient cytoplasmic drug delivery and gene transfection in human lung adenocarcinoma cell line A549. And in vivo investigation on nude mice bearing A549 tumor xenografts revealed that DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes possessed specific tumor targeting and strong antitumor activity. The work described here demonstrated that the DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes might offer a promising tool for effective cancer therapy.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Terapia Genética/métodos , Nanopartículas/química , Neoplasias/terapia , Animais , Humanos , Camundongos , Camundongos Nus , Neoplasias/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Calcitriol/administração & dosagem , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Calcitriol/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Lipossomos/química , Células MCF-7 , Campos Magnéticos , Camundongos Endogâmicos BALB C , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is highly resistant to currently available chemotherapeutic agents. The clinical outcome of HCC treatment remains unsatisfactory. Therefore, new effective and well-tolerated therapy strategies are needed. Natural products are excellent sources for the development of new medications for disease treatment. Recently, we and other researchers have suggested that the combined effect of natural products may improve the effect of chemotherapy treatments against the proliferation of cancer cells. In addition, many combination treatments with natural products augmented intracellular reactive oxygen species (ROS). In this review we will demonstrate the synergistic anticancer effects of a combination of natural products with chemotherapeutic agents or natural products against human HCC and provide new insight into the development of novel combination therapies against HCC.