Arsenic oxide targets stem cell marker CD133/prominin-1 in gallbladder carcinoma
2011
Ai, Zhilong | Pan, Hongtao | Suo, Tao | Lv, Chentao | Wang, Yueqi | Tong, Saixiong | Liu, Houbao
CD133⁺ tumor cells are responsible for the initiation, propagation and recurrence of tumors, which raises the question of how to effectively target CD133⁺ tumor cells. Arsenic trioxide (As₂O₃) has considerable efficacy in treating solid tumors with induction of apoptosis. Here, we found that purified CD133⁺ gallbladder carcinoma cells are highly resistant to conventional chemotherapy. However, As₂O₃ effectively induces CD133⁺ gallbladder carcinoma cells apoptosis. Treatment with As₂O₃ reduces CD133 expression at transcriptional levels. Furthermore, the ectopic expression of CD133 attenuated the apoptotic effect of As₂O₃ on cells through activation of AKT signaling pathways. Collectively, As₂O₃ effectively targets CD133 in gallbladder carcinoma, providing a new mechanism of As₂O₃-induced cell apoptosis and a better understanding of drug resistance in gallbladder carcinoma.
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