Apatinib increases anticancer potential of doxorubicin in breast cancer cells.

BACKGROUND: In recent years, drug resistance has become a most important challenge in chemotherapy of malignancies. Here, we investigated a novel approach to enhance therapeutic potential of doxorubicin (Dox as a common chemotherapeutic drug) by co-administration of apatinib (Apa as a monoclonal antibody) in breast cancer treatment. METHODS AND RESULTS: Effects of Apa, Dox, and their combinations (Apa-Dox) were investigated on proliferation of MDA-MB-231 breast cancer cells by MTT assay. Moreover, migration and invasion of the treated and untreated control cancer cells were evaluated by scratch and transwell methods, respectively. Apoptosis percentage of the treated cancer cells was investigated by flow cytometry method. Finally, apoptosis-, metastasis-, and angiogenesis-related gene expression at mRNA and protein levels in the cancer cells were investigated by Real-Time PCR and western blotting methods, respectively. Our results indicated that treatments of cancer cells by Apa, Dox, and Apa-Dox significantly decrease proliferation, migration, and invasion of MDA-MB-231 breast cancer cells. Treatments of the breast cancer cells by Apa, Dox, and Apa-Dox significantly increase apoptosis percentage. We observed that anticancer effects of Apa, Dox, and Apa-Dox may due to modification of apoptosis-, metastasis-, and angiogenesis-related gene expression (at mRNA and protein level) in the breast cancer cells. However, anticancer potential of Apa-Dox combination was significantly more than Apa and Dox monotherapy. CONCLUSION: We demonstrated that Apa significantly increases anticancer potential of Dox in MDA-MB-231 breast cells. However, further in-vitro, in-vivo, and clinical studies are required to confirm this result.

Enhanced anticancer potency of hydroxytyrosol and curcumin by PLGA-PAA nano-encapsulation on PANC-1 pancreatic cancer cell line.

Many chemotherapeutic regimens have been investigated for advanced unresectable and metastatic pancreatic cancer (PC), but with only minimal improvement in survival and prognosis. Here, we investigated anti-cancer function of free and nano-encapsulated hydroxytyrosol (Hyd) and curcumin (Cur), and its combinations (Hyd-Cur) on PANC-1 cell line. The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nano-encapsulated Hyd and Cur were synthesized, and MTT assay was performed to evaluate cytotoxic effects of free and nano-encapsulated Hyd, Cur, and Hyd-Cur. Effects of free and nano-encapsulated Hyd, Cur, and Hyd-Cur were evaluated on viability, migration, morphological alterations, colony formation, and apoptosis on PANC-1 cells. We observed that free and nano-encapsulated Hyd, Cur, and Hyd-Cur significantly increased apoptosis rates as well as significantly decreased viability, migration, and colony formation in PANC-1 cells. According to our results, Hyd-Cur combination and nano-encapsulation therapy exerts more profound apoptotic and anti-proliferative effects on PANC-1 cells than free Hyd or Hyd monotherapy.

Melatonin increases the anticancer potential of doxorubicin in Caco-2 colorectal cancer cells.

Colorectal cancer (CC) is an important human malignancy with high cancer related death worldwide. The chemotherapy using doxorubicin hydrochloride is one of the most common cancer therapeutic methods. However, drug resistance lowers the treatment efficacy in CC patients. The combination therapies seem to be more promising by taking the advantage of synergistic effects. The present study aimed to evaluate a new strategy to enhance the anticancer activity of doxorubicin in Caco-2 CC cell line by co-administration of melatonin. The effects of doxorubicin, melatonin, and their combinations (Dox-Mel) were investigated on the proliferation and viability, morphological alterations, and tumor spheroid formation. Flow cytometry was employed to compare the apoptotic situation of the cells in study groups. Changes in metastatic potential of the cells were assessed by wound healing assay and trans-well migration assays. Moreover, expression of BAX, SMAC, BCL-2, SURVIVIN, MMP-2, and MMP-9 genes were evaluated by quantitative real time PCR and western blotting. Our study showed that doxorubicin, melatonin, and Dox-Mel significantly decreased the proliferation and viability, tumor spheroid formation, invasion, and migration. Furthermore, the changes were in a concentration and time dependent manner. There was an increase in apoptosis rate in the treatment groups. Expression of genes involved in apoptosis and cell motility were altered significantly. It was observed that anticancer activity of Dox-Mel combination was significantly more than doxorubicin and melatonin treatments alone. We showed an enhanced apoptotic and anticancer activity of doxorubicin and melatonin combination chemotherapy on CC cell line than doxorubicin or melatonin treatments alone. This combination could promote the treatment efficiency and alleviate the un-intended side effects by lowering the dose of doxorubicin prescription.