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Article Publish Status: FREE
Abstract Title:

Chemosensitizing Effect and Efficacy of Wilforlide A in Combination With Docetaxel in Drug-resistant Prostate Cancer.

Abstract Source:

In Vivo. 2022 Sep-Oct;36(5):2020-2031. PMID: 36099129

Abstract Author(s):

Zhijun Wang, Steven Yeung, Shanchao Yang, Ying Huang, Moses Sing Sum Chow

Article Affiliation:

Zhijun Wang

Abstract:

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 ICin 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.

Study Type : In Vitro Study

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