Ping He, Changhua Zhou, Qing Li 

School of Pharmaceutical Sciences, Sun Yat-Sen University

Objective:This study was undertaken to evaluate the selective activation and targeted cell killing of AKR1C3-prodrug both in vitro and in vivo for liver cancer cells. Method: In vitro cytotoxicity was evaluated using human liver cancer cell lines. AKR1C3 expression was detected by western blot. Subsequently, human liver cancer xenograft model was performed to investigate the in vivo effect of AKR1C3 prodrugs. Result: i). TheAKR1C3-prodrugs cytotoxicity correlates with the expression level of AKR1C3 in liver cancer cells. The higher expression level of AKR1C3 in cancer cells, the lower IC50 of AKR1C3 pro-drug is. ii).Knock-down or inhibition of AKR1C3 reduces the cytotoxicity of AKR1C3 pro-drug. iii). Xenograft studies confirmed the efficacy of AKR1C3 pro-drug depends on the expression level of AKR1C3 in liver cancer cells. Conclusion: AKR1C3 pro-drug is a novel therapeutic strategy for tumors with over-expression of AKR1C3, especially HCC.

Key Words: AKR1C3 Pro-drug  Hepatocellular carcinoma