Polyphyllin I induces autophagy and cell cycle arrest via inhibiting PDK1/Akt/mTOR signal and downregulating cyclin B1 in human gastric carcinoma HGC-27 cells

被引：46

作者：

He, Junlin ^{[1
]}

Yu, Si ^{[1
,2
]}

Guo, Chuanjie ^{[1
]}

Tan, Lu ^{[1
]}

Song, Xiaominting ^{[1
]}

Wang, Miao ^{[1
]}

Wu, Jing ^{[1
]}

Long, Yuling ^{[1
]}

Gong, Daoyin ^{[1
]}

Zhang, Ruoqi ^{[1
]}

Can, Zhixing ^{[1
]}

Li, Yuzhi ^{[1
]}

Peng, Cheng ^{[1
]}

机构：

[1] Chengdu Univ Tradit Chinese Med, Sch Pharm, Key Lab Standardizat Chinese Herbal Med, Minist Educ,Natl Key Lab Breeding Base Systemat R, Chengdu 611137, Sichuan, Peoples R China

[2] Chengdu Med Coll, Chengdu 610500, Sichuan, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2019年 / 117卷

基金：

中国国家自然科学基金;

关键词：

Polyphyllin I; Gastric cancer; Autophagy; Cell cycle; PDK1/Akt/mTOR; CANCER CELLS; APOPTOSIS; PDK1; SAPONINS; DEATH;

D O I：

10.1016/j.biopha.2019.109189

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Paris polyphylla. is a traditional medicinal herb that has long been used to prevent cancer in many Asian countries. Polyphyllin I (PPI), an important bioactive constituent of Paris polyphylla, has been found to exhibit a wide variety of anticancer activities in many types of cancer cells. However, the effects of PPI on human gastric carcinoma cells and its mechanism of action remain unclear. In this study, we examined the effective anti-gastric carcinoma activity of PPI and its underlying mechanism of action in HGC-27 cells. In vitro, sub-micromolar concentrations of PPI inhibited HGC-27 cell proliferation with an IC50 of 0.34 +/- 0.06 mu M after a 72-h treatment. In vivo, 3 mg/kg PPI significantly inhibited proliferation of HGC-27 tumor cells, with a 78.8% inhibition rate compared to paclitaxel, and demonstrated higher safety. Analysis of MDC and mGFP-LC3 fluorescence, Western blotting and flow cytometry indicated that PPI induced cell cycle arrest in HGC-27 cells by promoting the conversion of LC3-I to LC3-II and by downregulating cyclin B1. Furthermore, Western blotting showed that PPI inhibited the autophagy-regulating PDK1/Akt/mTOR signaling pathway in vitro and in vivo. In addition, immunohistochemistry and TUNEL staining revealed that PPI decreased Ki67 expression and increased the percentage of apoptotic cells in HGC-27 xenograft tumors. These data indicate that PPI is an PDK1/Akt/mTOR signaling inhibitor and of therapeutic relevance for gastric cancer treatment and that the rhizome of Paris polyphylla deserves further clinical investigation as an alternative therapy for gastric cancer.

引用

页数：8

共 35 条

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