Hepatocellular carcinoma (HCC) is the second leading cause of
cancer related death which needs novel drugs to improve patient outcome.
Survivin overexpresses in HCC and contributes to HCC malignant progression. In this study, we established a
Survivin-targeted
drug screening platform, a cell model HepG2-Sur5P-EGFP-Sur3U stably transfected with lentivirus carrying an EGFP expression cassette, in which the EGFP expression was regulated by the upstream
Survivin promoter and downstream
Survivin 3'-UTR. By using this platform, we screened and easily identified one of
matrine derivatives, WM-127, from hundreds of
matrine derivatives. WM-127 was demonstrated to be a strong
Survivin inhibitor that inhibited cell proliferation, induced cell cycle arrest and apoptosis of HCC cells, and suppressed the growth of HCC xenografted
tumors in nude mice, suggesting that WM-127 might be a promising
drug for HCC treatment. WM-127 exhibited less cytotoxicity in normal cells. Mechanistic studies showed that WM-127 suppressed the activity of
Survivin/β-
catenin pathway and the expression of Bax to induce cell cycle arrest and apoptosis. Taken together, we constructed an economical, practical, efficient and convenient cell platform for screening the
Survivin-targeted drugs from the enormous diversity of chemicals or factors, which would be a potential tool for
antitumor drug research and development.