Study on the Mechanism of β-Sitosterol Regulating Ki67 in Anti-Prostate Cancer Effects

ZHAO Bin; ZHUANG Dongyang; XU Xiangdong; HUANG Wenwen

doi:10.16458/j.cnki.1007-0893.2025.17.004

Abstract：Objective To investigate the mechanism of action of the plant sterol β-sitosterol on prostate cancer and its selectivity for cells with different androgen receptor(AR)statuses,providing new evidence for the treatment of prostate cancer and the transformation and application of plant sterols.Methods PC-3 cells with AR-negative and 22RV1 cells with AR-positive were used as models.Cell counting kit-8(CCK-8)and colony formation assays were conducted to detect the inhibitory effect on proliferation.Apoptosis detection and cell cycle analysis were performed to reveal the cell cycle arrest and pro-apoptotic mechanisms.Immunofluorescence,enzyme-Linked immunosorbent assay(ELISA)and real-time quantitative reverse transcription polymerase Chain reaction(RT-qPCR)were used to comprehensively analyze the regulation of Ki67 expression.Zebrafish experiments were further conducted to verify its in vivo anti-tumor activity and safety.Results β-sitosterol inhibited the proliferation of PC-3 and 22RV1 cells in a dose-dependent manner,with PC-3 cells being more sensitive.It promoted early and late apoptosis in both cell types,arrested the cell cycle at the G0/G1 phase,and inhibited the expression of Ki67 protein.In zebrafish,it could suppress the growth of xenograft tumors.Conclusion β-sitosterol inhibits the malignant behavior of prostate cancer cells through multiple pathways,with good safety in both in vitro and in vivo settings,providing a basis for its development as a natural anti-cancer drug.