Effects Of Mitochondrial Dynamics On Hypoxia-induced Migration And Antineoplastic Activity Of Cisplatin In Breast Cancer Cells And Their Mechanisms

Breast cancer is one of the leading causes of death in women in the world, due to its morbidity and mortality. Mitochondria are highly dynamic organelles with two homeostasis process in frequent fission and fusion. Here, we reported that hypoxia promoted Drp1 expression, mitochondrial fission and migration in metastatic MDA-MB-231 cells, but not in non-metastatic MCF-7 cells. Further experimental study, inhibition of Drp1-dependent mitochondrial fission by mdivi-1 or silencing of Drp1 attenuated hypoxia-induced mitochondrial fission and migration in MDA-MB-231 cells. Our results also showed that cisplatin significantly induced apoptosis and mitochondrial fission in MDA-MB-231 cells, but not in MCF-7 cells. Mdivi-1 and silencing of Drp1 also efficiently prevented cisplatin-induced MMP decrease, ROS production and apoptosis in MDA-MB-231 cells. These results suggest that Drp1-dependent mitochondrial fission not only regulates hypoxia-induced migration of breast cancer cells, but also facilitates its sensitivity to chemotherapeutic agents CDDP. Thus, targeting Drp1-dependent mitochondrial dynamics may provide a novel strategy for suppressing breast cancer metastasis and improving the chemotherapeutic effects in the future.