Apatinib increases anticancer potential of doxorubicin in breast cancer cells.

ABSTRACT

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.