Resveratrol inhibits proliferation and promotes apoptosis via the androgen receptor splicing variant 7 and PI3K/AKT signaling pathway in LNCaP prostate cancer cells.

Abstract

Prostate cancer is a common malignant tumor of the male genitourinary system and its incidence increases with age. Studies have shown that resveratrol (Res) inhibits cancer cell proliferation, migration, invasion and promotes apoptosis. The present study evaluated the effect of Res in two human prostate cancer cell lines (the androgen-dependent LNCaP cell line and the non-androgen-independent LNCaP-B cell line) on proliferation and apoptosis. A proliferation assay was used to demonstrate that Res inhibited proliferation of LNCaP and LNCaP-B cells in the range of 25–100 µM, and the effect was time- and dose-dependent. Using flow cytometry, it was reported that various concentrations of Res induced apoptosis in LNCaP and LNCaP-B cells, and that the apoptotic effect of Res was dose-dependent. A chemiluminescence assay showed that Res inhibited prostate specific antigen levels in LNCaP and LNCaP-B cells. Reverse transcription quantitative-PCR showed that Res inhibited the expression of androgen receptor (AR) in LNCaP and LNCaP-B cells at the mRNA level. Western blot analysis showed that Res suppressed the expression of AR protein as well as protein kinase B (AKT) phosphorylation. To study the effect of Res on the expression of AR splicing variant 7 (ARV7) and the PI3K/AKT signaling pathway in prostate cancer cells, as well as the underlying molecular mechanisms, the recombinant ARV7 expression vector Pcdna3.1-ARV7 was transfected into LNCaP and LNCaP cells and the aforementioned experiments were repeated. It was revealed that Res acted via the ARV7 and the AKT pathways. Taken together, the present results suggested that Res suppresses the proliferation of prostate cancer cells, promotes apoptosis and inhibits the expression of AR mRNA and protein. These effects likely resulted from inhibition of ARV7 and the AKT signaling pathway.