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

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 properties 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 radiotherapy. 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.

[Preventive and therapeutic effects of xiaobanxia fuling decoction on cisplatin-induced pica rats].

OBJECTIVE: To investigate the preventive and therapeutic effects of Xiaobanxia Fuling Decoction (XBFD) on cisplatin-induced pica rats and to study its mechanism. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into the following 7 groups, i.e., the blank control group, the model group, the high-, middle-, and low-dose XBFD groups (at the daily dose of 30, 15, and 7. 5 g/kg, respectively), the aprepitant (at the daily dose of 13 mg/kg), and pure Chinese medicine group (at the daily dose of XBFD 15 g/kg), 6 in each group. On the 3rd day of this study, 3 mg/kg cisplatin was intraperitoneally injected to rats except the blank control group and the model group to establish the pica rat model. The consumptions of kaolin, food, and the general situation of rats were observed. The protein and mRNA expressions of neurokinin 1 receptor (NK1R) in both the medulla oblongata and the gastric antrum were measured by immunohistochemical assay and Real-time fluorescent quantitative PCR respectively on the sixth day of this study. RESULTS: On the third, fourth, and fifth day of this study, the consumption of kaolin of rats significantly increased when compared with the blank control group (P<0.01). Compared with the model group, the consumption of kaolin significantly decreased in the high-, middle-, and low-dose XBFD groups on the third, fourth, and fifth day of this study (P<0.05). The food intake of rats in the high-dose XBFD groups significantly increased when compared with the model group on the third day of this study (P<0.05). The protein and mRNA expressions of NK, R in the medulla oblongata and the gastric antrum significantly decreased in the high- and middle-dose XBFD groups when compared with the model group (P<0.05). CONCLUSIONS: XBFD could prevent and treat cisplatin-induced pica in rats. Its effect might be correlated with decreasing expressions of NK, R in the medulla oblongata and the gastric antrum.