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Cancer Biother Radiopharm. 2019 Mar 11. doi: 10.1089/cbr.2018.2559. [Epub ahead of print]

Inhibition of Autophagy Improves the Efficacy of Abiraterone for the Treatment of Prostate Cancer.

Author information

1
1 Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
2
2 Department of Prevention and Health Care, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Abstract

OBJECTIVES:

Although androgen deprivation therapy remains the standard treatment for the initial therapy of advanced prostate cancer (PC), castration does not eliminate persistent intratumoral androgens within the prostate tumor microenvironment, which is capable of activating androgen receptor. Abiraterone effectively target adrenal and tumor androgen production in castration-resistant PC (CRPC). However, abiraterone-resistant CRPC is now common challenge in clinic via multiple mechanisms.

METHODS:

In this study, human CRPC cell line PC3 and androgen-sensitive cells LNCaP were used. The authors investigated the role of autophagy during the therapy of abiraterone in CRPC by analysis of transmission electron microscopy (TEM), Western blot and immunofluorescence assay. Cell cycle and apoptosis using flow cytometry analysis.

RESULTS:

The analysis of TEM showed more autophagic vesicles (AVs) in PC3 cell line than that in LNCaP cell line and indicated the high basic cellular autophagy in CRPC cell line PC3, which was confirmed by the upregulation of autophagy-related protein LC3, Atg5, and Beclin1. Interestingly, the treatment of abiraterone reduced the level of autophagic vesicles in two cell lines and inhibited the expressions of autophagic markers LC3, Atg5 and Beclin1 in parallel with decreased cell vitality and induced G2/M arrest in PC3 cell line and LNCaP cell line. Moreover, the addition of the autophagy inhibitor 3-methyladenine to the treatment of abiraterone inhibited the formation of AVs with downregulated autophagic markers, and inhibition of autophagy promoted the efficiency of cytotoxicity of abiraterone with further impaired cell vitality and G2/M arrest.

CONCLUSION:

These data suggested that inhibition of autophagy by its inhibitor benefits the treatment of abiraterone for CRPC patients.

KEYWORDS:

CRPC; abiraterone; autophagy; prostate cancer

PMID:
30855185
DOI:
10.1089/cbr.2018.2559

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