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KMID : 1034820220180030359
Molecular & Cellular Toxicology
2022 Volume.18 No. 3 p.359 ~ p.369
Polyphyllin I combined with doxorubicin shows chemosensitization effect in vivo and reduces immunotoxicity of doxorubicin
Zhu Xiang

Na Xin
Zeng Yueqin
Xu Yangantai
Chai Dongya
Yang Huanzhi
Miao Jingqian
Zhang Yuan
Yang Fenghua
Wang Yuehu
Zhou Yiping
Abstract
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.
KEYWORD
Polyphyllin I, Chemosensitization, Doxorubicin, Immunotoxicity, Hemolysis
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