TY - JOUR T1 - Chemosensitizing Effect and Efficacy of Wilforlide A in Combination With Docetaxel in Drug-resistant Prostate Cancer JF - In Vivo JO - In Vivo SP - 2020 LP - 2031 DO - 10.21873/invivo.12928 VL - 36 IS - 5 AU - ZHIJUN WANG AU - STEVEN YEUNG AU - SHANCHAO YANG AU - YING HUANG AU - MOSES SING SUM CHOW Y1 - 2022/09/01 UR - http://iv.iiarjournals.org/content/36/5/2020.abstract N2 - Background/Aim: Prostate cancer is currently the second most common cancer in men and chemotherapy is the main treatment for metastatic castrate-resistant prostate cancers (mCRPC). However, chemoresistance leading to treatment failure is inevitable. Thus, therapeutic approaches that can overcome chemoresistance are important areas of research for cancer chemotherapy. Materials and Methods: In the present study, six components of tripterygium wilfordii including celastrol, triptolide, pristimerin, triptonide, demethylzeylasteral, and wilforlide A were screened for their chemosensitizing effect on drug-resistant prostate cancer cell lines PC3 and DU145. The most active compound was further investigated on its potential mechanism of action and in vivo efficacy using a SCID mouse model. Results: Among the six components only wilforlide A significantly enhanced sensitivity to docetaxel (by reducing the IC50 in resistant prostate cancer cell lines). Wilforlide A inhibited P-glycoprotein efflux transporter and downregulated cyclin E2 splice variant 1 mRNA, both have been known as mechanisms of resistance. The chemosensitizing effect was further verified using a xenograft mouse model. In the high-dose treatment group, the combination of wilforlide A and docetaxel significantly retarded tumor growth of resistant prostate cancer, although neither docetaxel nor wilforlide A monotreatment groups showed any effect. Conclusion: Wilforlide A was found to enhance the chemosensitizing effect of docetaxel both in vitro and in vivo. Further studies are warranted to verify wilforlide A as a new drug candidate to overcome docetaxel resistance in prostate cancer. ER -