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Zhu Xiang,Na Xin,Zeng Yueqin,Xu Yangantai,Chai Dongya,Yang Huanzhi,Miao Jingqian,Zhang Yuan,Yang Fenghua,Wang Yuehu,Zhou Yiping 대한독성 유전단백체 학회 2022 Molecular & cellular toxicology Vol.18 No.3
Background Polyphyllin I (PPI), a steroidal saponin, exhibits antitumor activity and chemosensitization effect for a broad spectrum of cancer cells, however, its toxicity and chemosensitization effect in vivo is still unknown. Objective We investigated PPI’s cytotoxic activity, toxicity and chemosensitization effect and in vitro and in vivo . Results The IC 50 values of PPI on MCF-7, H22, and S180 tumor cells were 4.37 μmol/L, 1.71 μmol/L, and 0.92 μmol/L, respectively. The LD 50 of PPI was found to be 47.9 mg/kg using ip. injection. PPI at concentrations of 0.3 mg/kg, 0.6 mg/ kg, 1.2 mg/kg, and 2.4 mg/kg (1/80 LD 50 –1/20 LD 50 ) were synergized with DOX of 0.5 mg/kg to inhibit the H22 and S180 tumor growth in vivo by inducing apoptosis without obvious immunotoxicity. PPI exhibited a remarkable hemolytic effect on rabbit erythrocytes (EC 50 = 4.3 μM), while it had no impact in mice. Conclusion Our study revealed that the PPI-sensitized chemotherapeutic effect, when used in safe doses, circumvents immunotoxic side effects of DOX in vivo; thus, helping future clinical research.