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西黄丸及其主要成分抑制PI3K/Akt/mTOR信号通路并促进荷PC-3肿瘤小鼠前列腺癌细胞的凋亡

[Xihuang Pills and its main components inhibit PI3K/Akt/mTOR signaling pathways and promote the apoptosis of prostate cancer cells in PC-3 tumor-bearing mice].

作者信息

Long Yan, Wu Yong-Rong, Guo Yin-Mei, Luo Xin-Jun, Li Xian-Fu, Huang Tian-Tian, Huang Zhen, Liu Zhuo, Chen Zheng-Jia, Zhou Qing, Tian Xue-Fei

机构信息

School of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.

Key Laboratory of TCM Prescriptions and Syndromes, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China.

出版信息

Zhonghua Nan Ke Xue. 2021 Apr;27(4):340-346.

PMID:34914218
Abstract

OBJECTIVE

To evaluate the effects of Xihuang Pills (XHP) and its main components on PI3K, AKT and mTOR signaling pathways and cell apoptosis of castration-resistant human PCa PC-3 cell subcutaneously transplanted tumors in nude mice.

METHODS

We assigned 36 PC-3 tumor-bearing model mice to six groups of equal numbers to be treated with XHP, musk, calculus bovis (CB), musk + CB and docetaxel, respectively. After 14 days of intervention, we calculated the tumor-inhibition rate in different groups, observed the morphology of the tumor cells by HE staining, determined the levels of PI3K, Akt and mTOR mRNA by RT-qPCR, and determined the expressions of PI3K, Akt and mTOR signaling pathways and caspase-3 and caspase-9 proteins by Western blot.

RESULTS

After 14 days of medication, the tumor-inhibition rates in the XHP, musk, CB, musk + CB and docetaxel groups were 29.67%, 5.52%, 7.26%, 12.88% and 6.26%, respectively. HE staining showed the formation of apoptotic bodies in the tumor tissues after intervention, especially in the XHP and musk + CB groups. The mRNA and phosphorylated protein expressions of PI3K, Akt and mTOR were significantly down-regulated (P < 0.01), and so were the expressions of caspase-3 and caspase-9 proteins in the XHP and musk + CB groups in comparison with the control (P < 0.01).

CONCLUSIONS

Xihuang Pills, musk and calculus bovis can inhibit the growth of castration-resistant human PCa PC-3 cell subcutaneously transplanted tumors, which is associated with their effects of suppressing the abnormally activated PI3K, Akt and mTOR signaling pathways and promoting the apoptosis of PCa PC3 cells.

摘要

目的

评估西黄丸(XHP)及其主要成分对裸鼠皮下移植的去势抵抗性人前列腺癌PC-3细胞PI3K、AKT和mTOR信号通路及细胞凋亡的影响。

方法

将36只荷PC-3肿瘤模型小鼠等分为6组,分别给予西黄丸、麝香、牛黄(CB)、麝香+牛黄及多西他赛治疗。干预14天后,计算不同组的肿瘤抑制率,通过HE染色观察肿瘤细胞形态,采用RT-qPCR检测PI3K、Akt和mTOR mRNA水平,通过蛋白质免疫印迹法检测PI3K、Akt和mTOR信号通路及半胱天冬酶-3和半胱天冬酶-9蛋白的表达。

结果

用药14天后,西黄丸、麝香、牛黄、麝香+牛黄及多西他赛组的肿瘤抑制率分别为29.67%、5.52%、7.26%、12.88%和6.26%。HE染色显示干预后肿瘤组织中出现凋亡小体,尤其是在西黄丸和麝香+牛黄组。与对照组相比,西黄丸和麝香+牛黄组中PI3K、Akt和mTOR的mRNA及磷酸化蛋白表达显著下调(P<0.01),半胱天冬酶-3和半胱天冬酶-9蛋白的表达也显著下调(P<0.01)。

结论

西黄丸、麝香和牛黄可抑制去势抵抗性人前列腺癌PC-3细胞皮下移植瘤的生长,这与其抑制异常激活的PI3K、Akt和mTOR信号通路及促进PCa PC3细胞凋亡的作用有关。

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