Correlation of ARHI upregulation with growth suppression and STAT3 inactivation in resveratrol-treated ovarian cancer cells.

Abstract

Aplysia ras homology member I/ARHI is known as ovarian cancer suppressor gene and potential inhibitor of signal transducer and activator of transcription 3/STAT3 signaling. Resveratrol suppresses growth and STAT3 activation of ovarian cancer cells, while its influence in ARHI expression remains unknown. The current study aims to elucidate the status of ARHI expression and its relevance with growth suppression and STAT3 inactivation of resveratrol-treated cells. ARHI expression patterns of three ovarian cancer cell lines (human CAOV-3, OVCAR-3 and rat NUTU-19) without and with 100 μM resveratrol treatment were checked by immunocytochemical staining, Western blotting and RT-PCR. The involvement of ARHI in the growth inhibition and STAT3 inactivation of resveratrol-treated OVCAR-3 cells was investigated by transfection of ARHI-specific siRNA. ARHI is expressed in low levels in three ovarian cancer cell lines, which is upregulated upon resveratrol treatment accompanied with growth arrest, extensive apoptosis, increased autophagic activity and inactivated STAT3 signaling. Specific siRNA transfection efficiently knocked down ARHI expression in resveratrol-treated CAOV-3 and OVCAR-3 cells and increased the total cell number in limited extents (P> 0.05) in comparison with that of resveratrol-treated ovarian cancer cells without any transfection or transfected with mock oligonucleotides. ARHI knockdown failed to prevent resveratrol-caused STAT3 inactivation and cell crisis. ARHI upregulation is another molecular event caused by resveratrol and one of the elements related with resveratrol's anti-ovarian cancer efficacy. Resveratrol may inactivate STAT3 signaling of ovarian cancer cells in ARHI unrelated pattern(s).