RBPJ contributes to acquired docetaxel resistance in prostate cancer cells

Our previous work has shown that depletion of recombination signal-binding protein J (RBPJ) results in reduced cell growth in prostate cancer cells. In this study, we aimed to investigate the function of RBPJ in the chemoresistance of prostate cancer. The expression of RBPJ was quantified in docetaxel-resistant and parental prostate cancer cells. Loss- and gain-of-function experiments were conducted to explore the regulatory role of RBPJ in prostate cancer sensitivity to docetaxel. The pro-apoptotic effect of RBPJ silencing was checked in docetaxel-resistant prostate cancer cells. We found that docetaxel-resistant PC3-DR and DU145-DR cells expressed 3–5-fold high levels of RBPJ than parental PC3 and DU145 cells. Short hairpin RNA-mediated knockdown of RBPJ inhibited cell proliferation and colony formation and reversed docetaxel resistance in docetaxel-resistant prostate cancer cells. In contrast, overexpression of RBPJ promoted cell growth, colony formation, and docetaxel resistance in parental prostate cancer cells. Downregulation of RBPJ induced apoptosis in docetaxel-resistant cells, which was accompanied by enhanced cleavage of caspase-3. In addition, RBPJ silencing or overexpression markedly modulated the expression of the Bcl-2 family members including Bcl-2, Bcl-xL, Mcl-1, Bax, and Bak. Altogether, RBPJ contributes to acquisition of docetaxel resistance in prostate cancer cells and may thus represent a potential target for overcoming chemotherapeutic resistance in this malignancy.