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中药配方七方化癥汤通过 HGF/c-Met 信号通路抑制肝癌转移。

Chinese herbal formula QHF inhibits hepatocellular carcinoma metastasis via HGF/c-Met signaling pathway.

机构信息

College of Medical Science, China Three Gorges University, Yichang, 443002, China; Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China.

College of Medical Science, China Three Gorges University, Yichang, 443002, China; Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, China.

出版信息

Biomed Pharmacother. 2020 Dec;132:110867. doi: 10.1016/j.biopha.2020.110867. Epub 2020 Oct 16.

Abstract

Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors, and high recurrence and metastasis are the major obstacles to successful treatment of HCC. Traditional Chinese medicine has little known and unique advantages in the treatment of HCC. Previous studies have confirmed that Chinese herbal formula Qingrejiedu (clears away heat and toxins), Huoxuehuayu (promotes blood flow to remove stasis) and Fuzhengguben (strengthens healthy qi and root) (QHF) has a significant effect on patients with advanced HCC, improves the quality of life and prolongs the survival time of patients significantly. In this study, we investigated the effect of QHF on proliferation, migration and invasion of human high metastatic hepatocellular carcinoma cell line HCCLM3 and its underlying mechanism. The results from our in vitro experiments showed that QHF has the ability to inhibit the proliferation by inducing G2/M phase cell cycle arrest and induce apoptosis. Moreover, QHF can also inhibit migration and invasion of HCCLM3 cells and the expression of the p-c-Met protein in HCCLM3 cells was down-regulated. c-Met is closely related to the metastasis of HCC, then we constructed a stable transfected cell line HepG2-met with high expression of c-Met by transfection. Further study in vivo revealed that c-Met gene will promote the growth of tumors and lung metastases in nude mice, and QHF intervention can reduce tumor lung metastases by inhibiting the HGF/c-Met signaling pathway. In conclusion, our study reveals that QHF can inhibit the proliferation, migration and invasion of HCCLM3, and this effect may be related to inhibiting HGF/c-Met signaling pathway.

摘要

肝细胞癌 (HCC) 是最常见的恶性肿瘤之一,高复发和转移是 HCC 成功治疗的主要障碍。中药在 HCC 的治疗中有鲜为人知的独特优势。既往研究证实,清热解毒、活血化瘀、扶正固本的中药方剂对晚期 HCC 患者具有显著疗效,可明显改善患者的生活质量,延长患者的生存时间。本研究旨在探讨 QHF 对人高转移性肝癌细胞系 HCCLM3 的增殖、迁移和侵袭的影响及其作用机制。体外实验结果表明,QHF 可通过诱导 G2/M 期细胞周期阻滞和促进细胞凋亡来抑制细胞增殖。此外,QHF 还可抑制 HCCLM3 细胞的迁移和侵袭,并下调 HCCLM3 细胞中 p-c-Met 蛋白的表达。c-Met 与 HCC 的转移密切相关,因此我们通过转染构建了高表达 c-Met 的稳定转染细胞系 HepG2-met。进一步的体内研究表明,c-Met 基因可促进裸鼠肿瘤的生长和肺转移,而 QHF 干预可通过抑制 HGF/c-Met 信号通路减少肿瘤肺转移。综上所述,本研究表明 QHF 可抑制 HCCLM3 的增殖、迁移和侵袭,其作用可能与抑制 HGF/c-Met 信号通路有关。

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