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苦参碱、氧化苦参碱及苦参总碱凝胶对宫颈癌的抑制作用及其机制

Anti-Cervical Cancer Role of Matrine, Oxymatrine and Sophora Flavescens Alkaloid Gels and its Mechanism.

作者信息

Zhou Yu Jie, Guo Ya Jie, Yang Xiao Li, Ou Zhou Luo

机构信息

Key Laboratory of Breast Cancer in Shanghai, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.

出版信息

J Cancer. 2018 Apr 6;9(8):1357-1364. doi: 10.7150/jca.22427. eCollection 2018.

Abstract

Cervical cancer is one of the leading severe malignancies throughout the world. Sophra flavescens alkaloid (SFA) gels, a compound Traditional Chinese Medicine, has been clinically used in China for many years. Its individual active ingredients are matrine and oxymatrine, which has been showed that they can restrain primary tumorigenesis, while the underlying molecular mechanisms of SFA gels in cervical cancer cells remain unclear. To detect the effect of SFA gels and its active ingredients, CCK-8 assay and colony assay were used on cervical cancer cells proliferation. Transwell assay was used to detect cancer cell migration. Apoptosis and cell cycle arrest were used to detect whether SFA gels effect the cervical cancer cells proliferation. Western blot was used to detect whether SFA gels regulate the cervical cancer cells via the suppression of AKT/mTOR signaling pathway. SFA gels can restrain cervical cancer cell proliferation, inhibit metastasis, induce cell cycle arrest in G2/M phase, induce cellular apoptosis through stimulation of Bax and E-cadherin, and suppression of Bcl-2, cyclin A, MMP2. Further study shows that SFA gels may regulate the cervical cancer cells via the suppression of AKT/mTOR signaling pathway. SFA gels, like its active ingredients, can restrain cervical cancer cells proliferation, suppress cervical cancer cell migration, induce the apoptosis and cell cycle arrest in cervical cancer cells. SFA gels may be a potential anti-tumor therapeutic agent for treating cervical cancer.

摘要

宫颈癌是全球主要的严重恶性肿瘤之一。苦参总碱(SFA)凝胶作为一种复方中药,在中国已临床应用多年。其主要活性成分是苦参碱和氧化苦参碱,已证实它们能抑制原发性肿瘤的发生,但其在宫颈癌细胞中的潜在分子机制仍不清楚。为检测SFA凝胶及其活性成分的作用,采用CCK-8法和集落形成实验检测宫颈癌细胞的增殖情况,用Transwell实验检测癌细胞的迁移能力,采用凋亡实验和细胞周期阻滞实验检测SFA凝胶是否影响宫颈癌细胞的增殖,用蛋白质免疫印迹法检测SFA凝胶是否通过抑制AKT/mTOR信号通路来调控宫颈癌细胞。SFA凝胶可抑制宫颈癌细胞增殖,抑制转移,诱导细胞周期阻滞于G2/M期,通过刺激Bax和E-钙黏蛋白、抑制Bcl-2、细胞周期蛋白A、基质金属蛋白酶2诱导细胞凋亡。进一步研究表明,SFA凝胶可能通过抑制AKT/mTOR信号通路调控宫颈癌细胞。SFA凝胶与其活性成分一样,能抑制宫颈癌细胞增殖,抑制宫颈癌细胞迁移,诱导宫颈癌细胞凋亡和细胞周期阻滞。SFA凝胶可能是一种治疗宫颈癌的潜在抗肿瘤治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c0/5929079/ebb0e7c16702/jcav09p1357g001.jpg

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