Jianpi-Huayu Formula Inhibits Development of Hepatocellular Carcinoma by Regulating Expression of miR-602, Which Targets the RASSF1A Gene
Jianpi-Huayu Formula Inhibits Development of Hepatocellular Carcinoma by Regulating Expression of miR-602, Which Targets the RASSF1A Gene
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健脾化瘀方通过调节RASSF1A基因miR-602的表达抑制肝细胞癌的发展
DOI：
10.1177/1534735419900804
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发表时间：
2020-02-01
影响因子：
2.9
通讯作者：
Wang, Changjun
中科院分区：
文献类型：
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作者：
Huang, Yajing;Zhou, Cheng;Wang, Changjun
健脾化瘀方是治疗原发性肝癌的有效方剂。然而，其潜在机制仍不清楚。在这篇文章中，我们采用裸鼠原位移植模型来探讨JPHY是否可以通过调节miR-602来抑制HCC的发展，miR-602靶向Ras相关结构域蛋白1A（RASSF 1A）通路。用JPHY处理HCC SMMC-7721细胞以测试由miR-602介导的RASSF 1A基因是否影响肿瘤细胞的增殖和凋亡。我们随后在细胞和肝肿瘤组织中检测了miR-602、RASSF 1A和肿瘤细胞凋亡相关标志物。我们观察到用JPHY治疗的小鼠比未治疗的小鼠具有更小的肿瘤和更高的存活率。同样，JPHY处理的SMMC-7721细胞与对照组相比，表现出形态学的改变和更高的细胞毒性。此外，我们发现JPHY降低了miR-602的过表达，并增加了RASS 1A基因的蛋白表达水平，这反过来又改变了药物治疗小鼠的细胞和肝脏肿瘤组织中肿瘤细胞凋亡相关基因的蛋白表达水平。这些结果表明，JPHY可能通过靶向miR-602来治疗HCC，miR-602靶向RASSF 1A基因，而RASSF 1A基因在HCC发病机制中起主要作用。
The traditional Chinese medicine formula Jianpi-Huayu (JPHY) has been reported to be effective in the treatment of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. In this article, we employed an orthotopic transplantation model in nude mice to explore whether JPHY could inhibit the development of HCC by regulating miR-602, which targets the Ras association domain-containing protein 1A (RASSF1A) pathway. HCC SMMC-7721 cells were treated with JPHY to test whether the RASSF1A gene as mediated by miR-602 affected the proliferation and apoptosis of tumor cells. We subsequently detected miR-602, RASSF1A, and tumor cell apoptosis–related markers in cells and liver tumor tissues. We observed that mice treated with JPHY had smaller tumors and higher survival rates than untreated ones. Similarly, JPHY-treated SMMC-7721 cells exhibited alterations in morphology and higher cytotoxicity compared with the control group. Furthermore, we found that JPHY decreased overexpression of miR-602 and increased protein expression levels of the RASS1A gene, which in turn altered protein expression levels of tumor cell apoptosis–related genes in the cells and liver tumor tissues of drug-treated mice. These results indicated that JPHY could potentially be used to treat HCC by targeting miR-602, which targets the RASSF1A gene, which in turn plays a major role in HCC pathogenesis.