Mechanism of Total Flavonoids of Ampelopsis Grossedentata in Inhibiting Liver Cancer by PI3K/Akt/p53 Pathway
10.13422/j.cnki.syfjx.20190422
- VernacularTitle: 从PI3K/Akt/p53通路探讨藤茶总黄酮抗肝癌的作用机制
- Author:
Cai-yu GAN
1
;
Zuo-wen ZHENG
1
;
Bing-jie LIANG
1
;
Yun-li TANG
1
;
Wen-tao ZHANG
1
Author Information
1. Guangxi University of Chinese Medicine, Nanning 530001, China
- Publication Type:Research Article
- Keywords:
total flavonoids from ampelopsis grossedentata;
anti-liver cancer;
phosphatidylinositol 3 kinase (PI3K)/protein kinases B(Akt)/p53 signaling pathway;
mechanism of action
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(12):90-96
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To study inhibitory effect of total flavonoids from Ampelopsis grossedentata (TF) on transplanted tumors of human hepatocellular carcinoma in nude mice, and predict that its mechanism may be related to relevant factors regulating phosphatidylinositol 3 kinase (PI3K)/protein kinases B(Akt)/p53 pathway in apoptosis. Method: The nude mice transplanted BEL-7404 hepatoma model was established and divided into model group, 5-fluorouracil (5-FU) group (1.0 g·L-1) and TF (30, 15, 7.5 g·L-1) groups. Nude mice were put to death after two weeks of administration. The tumor tissues were excised, and tumor inhibition rate (IR) and relative tumor proliferation rate (T/C) were calculated. Reverse transcription PCR(RT-PCR) was used to detect PI3K, Akt1, p53 gene(p53), Caspase-3, B cell lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax) mRNA expressions, immunohistochemical method was used to detect expressions of relevant proteins PI3K, Akt1, p53, Caspase-3, Bcl-2, Bax. Result: The establishment of xenograft tumor in mice showed that TF was administered orally once per day for two consecutive weeks. IRs were 53.26%, 35.94%, and 26.74%, respectively. T/Cs were 59.74%, 69.66%, and 84.82%, respectively. RT-PCR experiments showed that compared with model group, when TF concentration was 30 g ·L-1, mRNA expressions of PI3K, Akt1, and Bcl-2 were significantly down-regulated, and mRNA expressions of tumor suppressor genes p53, Capsase-3, and Bax were significantly up-regulated. Immunohistochemical method results showed that compared with model group, at TF concentrations of 30, 15 g·L-1, all PI3K, Akt1, Bcl-2 protein expressions were significantly down-regulated, while p53, Capsase-3, Bax protein expressions were significantly increased. Conclusion: TF has an obvious anti-liver cancer activity in vivo. Its mechanism may be correlated with up-regulation of expressions of p53, Caspase-3, and activation of apoptosis PI3K/Akt/p53 pathway, thereby inhibiting Bcl-2, increasing expression of Bax, and promoting hepatocellular apoptosis.
