Role of Bcl-2 on drug resistance in breast cancer polyploidy-induced spindle poisons.

Abstract

Spindle poisons are chemotherapeutic drugs used in the treatment of malignant tumors; however, numerous patients develop resistance following chemotherapy. The present study aimed to induce polyploidy in breast cancer cells using the spindle poison nocodazole to investigate the mechanism of polyploid-induced tumor resistance. It was revealed that the spindle poison nocodazole induced apoptosis in HCC1806 cells but also induced polyploidy in MDA-MB-231 cells. The drug sensitivities of the polyploid MDA-MB-231 cells to paclitaxel, docetaxel, epirubicin, 5-fluorouracil and oxaliplatin were lower than those of the original tumor cells; however, the polyploid MDA-MB-231 cells were more sensitive to etoposide than the original tumor cells. The expression of F-box and WD repeat domain containing 7 (FBW7) was decreased, while the expression of MCL1 apoptosis regulator BCL2 family member (MCL-1) and Bcl-2 was increased, and caspase-3/9 and Bax were not expressed in MDA-MB-231 cells. The resistance to docetaxel and etoposide was reversed, but the sensitivity of paclitaxel was not changed following Bcl-2 silencing. The formation of polyploidy in tumors may be one of the molecular mechanisms underlying tumor resistance to spindle poisons. Expression of the Bcl-2 family members, for example FBW7 and MCL-1, plays a key role in apoptosis and the cell escape process that forms polyploid cells. However, Bcl-2 silencing has different reversal effects on different anti-tumor drugs, which requires further investigation.