Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats

Author(s)

Goncalves, Bianca Facchim ^[1] ; Pegorin de Campos, Silvana Gisele ^[2] ; Favaro, Wagner Jose ^[3] ; Brandt, Joyce Zalotti ^[1] ; Pinho, Cristiane Figueiredo ^[1] ; Justulin, Luis Antonio ^[1] ; Taboga, Sebastiao Roberto ^[2] ; Scarano, Wellerson Rodrigo ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Inst Biosci, Dept Morphol, Rua Prof Doutor Antonio Celso Wagner Zanin 250, BR-18618689 Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Inst Biosci Humanities & Exact Sci, Sao Jose Do Rio Preto, SP - Brazil

^[3] Univ Campinas UNICAMP, Inst Biol, Campinas, SP - Brazil

• Document type: Journal article
• Source: HORMONES & CANCER; v. 9, n. 3, p. 175-187, JUN 2018.
• Web of Science Citations: 2

Abstract

Use of drug combinations that target different pathways involved in the development and progression of prostate cancer (PCa) has emerged as an alternative to overcome the resistance caused by drug monotherapies. The antiandrogen abiraterone acetate and the PI3K/Akt inhibitor NVP-BEZ235 (BEZ235) may be suitable options for the prevention of drug resistance and the inhibition of PCa progression. The aim of the present study was to evaluate whether abiraterone acetate and BEZ235 achieve superior therapeutic effects to either drug administered as monotherapy, in the early stages of PCa in an androgen-dependent system. Our study showed that each drug might impair tumor growth by reducing proliferation and increasing cell death when administered as monotherapy. However, tumor growth continued to progress with each drug monotherapy and some important side effects were related to BEZ. Conversely, when used in combination, the drugs impaired the inflammatory response, decreased hyperplastic lesions, and blocked tumor progression from premalignant to a malignant stage. Our data showed that the strategy to block the androgenic and PI3K/AKT/mTOR pathway is an effective therapeutic option and should be investigated including distinct PI3K pathway inhibitors. (AU)

• FAPESP's process: 14/14202-7 - Experimental prostatic carcinogenesis: molecular targets and therapeutic perspectives
• Grantee: Wellerson Rodrigo Scarano
• Support type: Regular Research Grants
• FAPESP's process: 13/22604-5 - Synergistic effect of abiraterone acetate and PI3K/mTORC1/2 inhibitor (NVP-BEZ235) on prostate carcinogenesis in Fischer 344 rats
• Grantee: Bianca Facchim Gonçalves
• Support type: Scholarships in Brazil - Post-Doctorate