Chinese herbal formula QHF inhibits hepatocellular carcinoma metastasis via HGF/c-Met signaling pathway
Chinese herbal formula QHF inhibits hepatocellular carcinoma metastasis via HGF/c-Met signaling pathway
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中药QHF通过HGF/c-Met信号通路抑制肝癌转移
DOI：
10.1016/j.biopha.2020.110867
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发表时间：
2020
影响因子：
7.5
通讯作者：
Chen Tao
中科院分区：
文献类型：
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作者：
Yuan Shenjun;Gong Yuyuan;Chen Ruobing;Du Juan;Zhang Hongfeng;Chen Tao
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。中医药在肝癌治疗方面有着鲜为人知且独特的优势。既往研究证实，清热解毒、活血化瘀、扶正固本等中药方剂对晚期肝癌患者疗效显着，可显着提高患者的生活质量，延长患者的生存时间。在本研究中，我们探讨了QHF对人高转移性肝癌细胞系HCCLM3增殖、迁移和侵袭的影响及其潜在机制。我们的体外实验结果表明QHF具有通过诱导G2/M期细胞周期阻滞来抑制增殖并诱导细胞凋亡的能力。此外，QHF还可以抑制HCCLM3细胞的迁移和侵袭，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。进一步的体内研究发现，c-Met基因会促进裸鼠肿瘤的生长和肺转移，QHF干预可以通过抑制HGF/c-Met信号通路来减少肿瘤肺转移。总之，我们的研究表明QHF可以抑制HCCLM3的增殖、迁移和侵袭，这种作用可能与抑制HGF/c-Met信号通路有关。
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 Fuz-hengguben (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.