CD133 silencing inhibits stemness properties and enhances chemoradiosensitivity in CD133-positive liver cancer stem cells

Abstract

Cancer stem cells (CSCs) are considered the source of the initial tumor formation and postoperative recurrence and metastasis. CD133+ cells in hepatocellular carcinoma (HCC) display cancer stem-like properties and are thought to be responsible for chemoradioresistance. To explore the functional role of CD133 in liver cancer stem cells (LCSCs), we isolated CD133+ cells from the HCC cell line HepG2, which were tested and confirmed to be CSC-like cells in HCC, downregulated CD133 expression in HepG2-CD133+ cells by lentivirus-mediated short hairpin (shRNA) and analyzed the effects of CD133 on the modulation of stemness proper-ties and chemoradiosensitivity in LCSCs. Our results showed that the in vitro cell proliferation, tumorsphere formation, colony formation and in vivo tumor growth in NOD/SCID mouse xenografts of LCSCs were significantly repressed after CD133 silencing. We also found that suppression of CD133 enhances the sensitivity of LCSCs to chemotherapy and radio-therapy. Knockdown of CD133 reduced G0/G1 phase cells and increased cellular apoptosis via modulation of Bcl-2 and Bax. Collectively, the stem-targeted therapy via CD133 could provide a novel strategy for the treatment of HCC.