Polyphyllin I Promoted Melanoma Cells Autophagy and Apoptosis via PI3K/Akt/mTOR Signaling Pathway

被引:42
作者
Long, Jianwen [1 ,2 ]
Pi, Xianming [1 ]
机构
[1] Hubei Prov Acad Tradit Chinese Med, Hubei Prov Hosp Tradit Chinese Med, Dept Dermatol, Wuhan 430061, Peoples R China
[2] Hubei Univ Chinese Med, Clin Sch 1, Dept Dermatol, Wuhan 430061, Peoples R China
关键词
CANCER; PHOSPHORYLATION; PROLIFERATION; ACTIVATION;
D O I
10.1155/2020/5149417
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
To investigate whether Polyphyllin I (PPI) might induce the autophagy and apoptosis of melanoma cells by regulating PI3K/Akt/mTOR signal pathway. Melanoma A375 cells were incubated with different concentrations of Polyphyllin I (0, 1.5, 3.0, and 6.0 mg/L) and PI3K/Akt/mTOR signaling pathway activator IGF-1(20 mg/L). CCK-8 assay was utilized to detect cell proliferation; Cell apoptosis and cell cycle were measured by flow cytometry; Western blot was used to examine the expressions of proteins. Immunofluorescence analysis was performed to evaluate autophagy of A375 cells; In addition, xenograft-bearing nude mice were applied to study the role of Polyphyllin I on melanoma development, melanoma cell proliferation, as well as melanoma cell apoptosis in vivo. The outcomes represented that Polyphyllin I promoted A375 cell apoptosis via upregulating Bax level and cleaved caspase-3 level and downregulating Bcl-2 level, inhibited the growth of A375 cells at the G0/G1 phase, and enhanced cell autophagy via regulating the levels of Beclin 1, LC3II, and p62. However, IGF-1 (an activator of PI3K/Akt/mTOR signal pathway) attenuated these changes that Polyphyllin I induced. Furthermore, the xenograft model experiment confirmed that Polyphyllin I treatment suppressed xenograft tumor growth, increased apoptotic index evaluated by the TUNEL method, and reduced the level of Ki67 in tumor tissues in vivo. In conclusion, Polyphyllin I treatment enhanced melanoma cell autophagy and apoptosis, as well as blocked melanoma cell cycle via suppressing PI3K/Akt/mTOR signal pathway. Meanwhile, Polyphyllin I treatment suppressed the development of melanoma in vivo. Therefore, Polyphyllin I possibly is a promising molecular targeted agent used in melanoma therapy.
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页数:9
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