Inhibition of CDK9 sensitizes multidrug resistant ovarian cancer cells to paclitaxel

Multidrug resistance is the major cause of treatment failure in ovarian cancer. Overexpression of cyclin-dependent kinase (CDK) 9 has been observed in a variety of cancers and promotes tumor cell growth and proliferation by regulating transcription. However, the role of CDK9 in drug resistance of ovarian cancer remains unknown. In this study, the expression levels of CDK9 and related proteins were evaluated in two pairs of human ovarian cancer drug-resistant cell lines by western blot. We found that both drug resistant ovarian cancer cells expressed higher levels of CDK9 as compared with their parental drug sensitive cell lines. Additionally, inhibition of CDK9, with either siRNA or a CDK9 inhibitor LDC067, enhanced paclitaxel sensitivity in drug resistant ovarian cancer cells. This was also accompanied with a reduction in the phosphorylation of RNA polymerase II and Stat3, resulting in enhanced apoptosis. Furthermore, inhibition of CDK9 also decreased ovarian cancer spheroid formation and cell motility. These findings collectively indicate that inhibition of CDK9 can enhance paclitaxel sensitivity in drug resistant ovarian cancer cells by increasing apoptosis. CDK9 represents a promising target for overcome drug resistance in ovarian cancer.