Coptisine Induces Apoptosis in Human Hepatoma Cells Through Activating 67-kDa Laminin Receptor/cGMP Signaling.
Coptisine Induces Apoptosis in Human Hepatoma Cells Through Activating 67-kDa Laminin Receptor/cGMP Signaling.
复制标题
黄连碱通过激活 67-kDa 层粘连蛋白受体/cGMP 信号传导诱导人肝癌细胞凋亡
DOI：
10.3389/fphar.2018.00517
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发表时间：
2018
影响因子：
5.6
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Zhou L;Yang F;Li G;Huang J;Liu Y;Zhang Q;Tang Q;Hu C;Zhang R
肝细胞癌（HCC）是最常见的原发性肝癌。因此，迫切需要开发新的抗肝癌治疗策略。黄连碱是从黄连中提取的一种天然生物碱，在包括肝癌在内的多种临床前模型中表现出抗癌活性。然而，黄连碱抗肝癌作用的分子机制尚不清楚。我们使用流式细胞术评估黄连碱与SMMC 7721、HepG 2、LO 2和H9细胞表面表达的67 LR的结合。然后用黄连碱处理肝癌细胞系SMMC 7721、HepG 2和BEL 7402。使用细胞计数试剂盒-8测定法检测细胞活力。采用流式细胞术和转移酶介导的dUTP缺口末端标记（TUNEL）法检测细胞凋亡。Western blot检测凋亡相关蛋白和肿瘤死亡受体67-kDa层粘连蛋白受体（67 LR）。采用酶联免疫吸附法测定环鸟苷酸（cGMP）浓度。使用sh 67 LR慢病毒、抗67 LR抗体和cGMP抑制剂NS 2028来确定67 LR/cGMP信号通路如何调节黄连碱诱导的细胞凋亡。在SMMC 7721细胞异种移植小鼠模型中证实了黄连碱抑制肿瘤生长。黄连碱在人肝癌细胞中选择性地表现出细胞活力，但在正常人肝细胞系LO 2细胞中不表现出细胞活力。黄连碱通过增加67 LR活性促进SMMC 7721和HepG 2细胞凋亡。67 LR抗体和sh 67 LR处理都阻断了黄连碱诱导的细胞凋亡和细胞活力的抑制。黄连碱上调cGMP的表达。此外，cGMP抑制剂NS 2028显着降低黄连碱诱导的细胞凋亡和抑制细胞活力。体内实验证实黄连碱可通过67 LR/cGMP途径抑制SMMC 7721移植瘤的生长并诱导其凋亡。黄连碱介导的67 LR激活可能是治疗肝脏恶性肿瘤的新策略。
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Hence, new anti-liver cancer treatment strategies need to be urgently developed. Coptisine is a natural alkaloid extracted from rhizoma coptidis which exhibits anticancer activity in various preclinical models, including liver cancer. However, the molecular mechanisms underlying the anti-liver cancer effects of coptisine remains unclear. We used flow cytometry to assess the binding of coptisine to 67LR expressed on the surface of SMMC7721, HepG2, LO2 and H9 cells. Then SMMC7721, HepG2 and BEL7402 cells, belonging to the HCC cell lines, were treated with coptisine. The cell viability was detected using a cell counting kit-8 assay. Apoptosis was evaluated using flow cytometry and transferase-mediated dUTP nick-end labeling (TUNEL) assay. Apoptotic-related proteins and tumor death receptor 67-kDa laminin receptor (67LR) were detected using Western blot analysis. The cyclic guanosine 3′,5′-monophosphate (cGMP) concentration was determined using enzyme-linked immunosorbent assay. sh67LR lentivirus, anti67LR antibody, and cGMP inhibitor NS2028 were used to determine how a 67LR/cGMP signaling pathway regulated coptisine-induced apoptosis. Tumor growth inhibited by coptisine was confirmed in a SMMC7721 cell xenograft mouse model. Coptisine selectively exhibited cell viability in human hepatoma cells but not in normal human hepatocyte cell line LO2 cells. Coptisine promoted SMMC7721 and HepG2 cell apoptosis by increasing 67LR activity. Both 67LR antibody and sh67LR treatment blocked coptisine-induced apoptosis and inhibition of cell viability. Coptisine upregulated the expression of cGMP. Moreover, cGMP inhibitor NS2028 significantly decreased coptisine-induced apoptosis and inhibition of cell viability. In vivo experiments confirmed that coptisine could significantly suppress the tumor growth and induce apoptosis in SMMC7721 xenografts through a 67LR/cGMP pathway. Coptisine-mediated 67LR activation may be a new therapeutic strategy for treating hepatic malignancy.
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DOI：
10.1111/j.1440-1681.2004.03951.x
发表时间：
2004-01-01
影响因子：
2.9
作者：
Lin, CC;Ng, LT;Chiang, LC
通讯作者：
Chiang, LC
钙调神经磷酸酶 1 基因亚型 4 的调节剂，在肝细胞癌中下调，通过抑制 NFAT1 的核转位来防止癌细胞的增殖、迁移和侵袭活性以及原位肿瘤的转移
影响因子：
29.4
作者：
Jin, Haojie;Wang, Cun;Qin, Wenxin
通讯作者：
Qin, Wenxin
影响因子：
8.5
作者：
Saravani, R.;Karami-Tehrani, F.;Edalat, R.
通讯作者：
Edalat, R.
影响因子：
15.9
作者：
Kumazoe, Motofumi;Sugihara, Kaori;Tachibana, Hirofumi
通讯作者：
Tachibana, Hirofumi
影响因子：
5.2
作者：
Lu, Xin-Lan;Zeng, Jin;He, Shui-Xiang
通讯作者：
He, Shui-Xiang