KMID : 1034820220180030359
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Molecular & Cellular Toxicology 2022 Volume.18 No. 3 p.359 ~ p.369
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Polyphyllin I combined with doxorubicin shows chemosensitization effect in vivo and reduces immunotoxicity of doxorubicin
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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
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Abstract
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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 IC50 values of PPI on MCF-7, H22, and S180 tumor cells were 4.37 ¥ìmol/L, 1.71 ¥ìmol/L, and 0.92 ¥ìmol/L, respectively. The LD50 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 LD50?1/20 LD50) 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 (EC50 = 4.3 ¥ìM), 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.
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KEYWORD
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Polyphyllin I, Chemosensitization, Doxorubicin, Immunotoxicity, Hemolysis
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