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姜黄素通过调控和途径抑制肝癌的进展。

Extract of L. Inhibits the Progression of Hepatocellular Carcinoma by Regulating and Pathway.

机构信息

Traditional Chinese Medicine, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China.

State Institution of Drug Clinical Trials, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China.

出版信息

Cancer Biother Radiopharm. 2020 Oct;35(8):586-595. doi: 10.1089/cbr.2019.3229. Epub 2020 Jun 2.

DOI:10.1089/cbr.2019.3229
PMID:32486841
Abstract

Hepatocellular carcinoma (HCC) poses a growing threat to humans due to poor prognosis. Extract of L. (ESC) is reported to inhibit metastasis of HCC. However, the underlying mechanism of ESC in regulating the progression of HCC needs to be further investigated. 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure cell proliferation. Flow cytometry was employed to check cell apoptosis. Transwell assay was conducted to assess the abilities of cell migration and invasion. The protein levels of proliferating cell nuclear antigen, cleaved caspase 3 (c-caspase 3), E-cadherin, janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 were detected by Western blot. The interaction between and JAK1 was predicted by starBase, which was verified by the dual-luciferase reporter assay and RNA pull-down assay. The messenger RNA levels of and JAK1 were determined by quantitative real-time polymerase chain reaction. The results showed that the higher concentration or the longer time treatment of ESC led to the lower survival rate of HCC cells. Besides, ESC induced apoptosis and impeded migration and invasion of HCC cells. Moreover, downregulation of inverted the effects of ESC-mediated repression on HCC progression. Further studies indicated that targeted the 3'-untranslated region (3'UTR) of JAK1 and reversed JAK1-mediated impacts on HCC progression. Simultaneously, ESC inactivated pathway by regulating the expression of . ESC suppressed HCC progression by upregulating the expression of and blocking pathway.

摘要

肝细胞癌(HCC)由于预后不良,对人类构成了日益严重的威胁。据报道,L.(ESC)提取物可抑制 HCC 的转移。然而,ESC 调节 HCC 进展的潜在机制仍需进一步研究。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)测定法用于测量细胞增殖。流式细胞术用于检查细胞凋亡。Transwell 测定法用于评估细胞迁移和侵袭的能力。通过 Western blot 检测增殖细胞核抗原、裂解的半胱氨酸天冬氨酸蛋白酶 3(c-caspase 3)、E-钙黏蛋白、Janus 激酶 1(JAK1)、信号转导和转录激活因子 3(STAT3)和磷酸化 STAT3 的蛋白水平。starBase 预测了 与 JAK1 之间的相互作用,通过双荧光素酶报告基因检测和 RNA 下拉实验验证。通过定量实时聚合酶链反应确定 和 JAK1 的信使 RNA 水平。结果表明,ESC 的较高浓度或较长时间处理导致 HCC 细胞的存活率降低。此外,ESC 诱导 HCC 细胞凋亡并阻碍其迁移和侵袭。此外,下调 逆转了 ESC 介导的对 HCC 进展的抑制作用。进一步的研究表明, 靶向 JAK1 的 3'-非翻译区(3'UTR)并逆转了 JAK1 对 HCC 进展的影响。同时,ESC 通过调节 的表达使 通路失活。ESC 通过上调 的表达并阻断 通路来抑制 HCC 进展。

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