Mechanism of Total Flavonoids of Ampelopsis Grossedentata in Inhibiting Liver Cancer by PI3K/Akt/p53 Pathway

Cai-yu GAN; Zuo-wen ZHENG; Bing-jie LIANG; Yun-li TANG; Wen-tao ZHANG

doi:10.13422/j.cnki.syfjx.20190422

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Mechanism of Total Flavonoids of Ampelopsis Grossedentata in Inhibiting Liver Cancer by PI3K/Akt/p53 Pathway

Pharmacology | 更新时间：2021-02-09

- Mechanism of Total Flavonoids of Ampelopsis Grossedentata in Inhibiting Liver Cancer by PI3K/Akt/p53 Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 12, Pages: 90-96(2019)
- 作者机构：
  
  广西中医药大学，南宁　 530001
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190422
  CLC： R22; R242; R2-031; R285.5; R273
- Received：21 June 2018，
  
  Published Online：05 November 2018，
  
  Published：20 June 2019
- 稿件说明：
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Cai-yu GAN, Zuo-wen ZHENG, Bing-jie LIANG, et al. Mechanism of Total Flavonoids of Ampelopsis Grossedentata in Inhibiting Liver Cancer by PI3K/Akt/p53 Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(12): 90-96.
DOI：

Cai-yu GAN, Zuo-wen ZHENG, Bing-jie LIANG, et al. Mechanism of Total Flavonoids of Ampelopsis Grossedentata in Inhibiting Liver Cancer by PI3K/Akt/p53 Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(12): 90-96. DOI： 10.13422/j.cnki.syfjx.20190422.

摘要

目的：

研究藤茶总黄酮(TF)对肝癌裸鼠移植瘤的抑制作用，预测其作用机制可能与调控细胞凋亡肌醇磷脂-3-激酶/蛋白激酶B/p53(PI3K/Akt/p53)通路的相关因子有关。

方法：

建立BEL-7404肝癌裸鼠移植瘤模型，实验分为模型组，5-氟尿嘧啶(5-FU，1.0 g·L

－1

)组及TF高、中、低质量浓度(30，15，7.5 g·L

－1

)组，给药干预2周后处死裸鼠，剥离出瘤组织，根据瘤重和瘤体积计算抑瘤率(IR)及相对肿瘤增殖率(T/C)；采用逆转录聚合酶链式反应(RT-PCR)检测PI3K/Akt/p53中相关基因胞内PI3K，Akt1，p53，半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)，B细胞淋巴瘤/白血病-2(Bcl-2)，Bcl-2相关X蛋白(Bax) mRNA表达；采用免疫组化检测相关蛋白PI3K，Akt1，p53，Caspase-3，Bcl-2，Bax蛋白的表达。

结果：

TF高、中、低质量浓度组IR分别为53.26%，35.94%，26.74%，T/C分别为59.74%，69.66%，84.82%；逆转录聚合本科链式反应(RT-PCR)表明，与模型组比较，TF 30 g·L

－1

能明显下调PI3K，Akt1，Bcl-2 mRNA表达，显著上调抑癌基因p53，Capsase-3，Bax mRNA表达；免疫组化表明，与模型组比较，TF 30，15 g·L

－1

均明显下调PI3K，Akt1，Bcl-2蛋白的表达，显著上调p53，Capsase-3，Bax蛋白的表达。

结论：

TF有明显的体内抗肝癌活性，其机制可能与上调p53，Caspase-3的表达，激活细胞凋亡PI3K/Akt/p53通路，从而抑制Bcl-2，提高Bax的表达，促进肝癌细胞凋亡有关。

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

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.

关键词

Keywords

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