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Hydroxysteroid Sulfotransferase SULT2B1b Promotes Hepatocellular Carcinoma Cells Proliferation In Vitro and In Vivo

机译:羟基类固醇硫转移酶SULT2B1b促进肝癌细胞的体内和体外增殖。

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摘要

Hydroxysteroid sulfotransferase 2B1b (SULT2B1b) is highly selective for the addition of sulfate groups to 3β-hydroxysteroids. Although previous reports have suggested that SULT2B1b is correlated with cell proliferation of hepatocytes, the relationship between SULT2B1b and the malignant phenotype of hepatocarcinoma cells was not clear. In the present study, we found that SULT2B1 was comparatively higher in the human hepatocarcinoma tumorous tissues than their adjacent tissues. Besides, SULT2B1b overexpression promoted the growth of the mouse hepatocarcinoma cell line Hepa1-6, while Lentivirus-mediated SULT2B1b interference inhibited growth as assessed by the CCK-8 assay. Likewise, inhibition of SULT2B1b expression induced cell-cycle arrest and apoptosis in Hepa1-6 cells by upregulating the expression of FAS, downregulating the expression of cyclinB1, BCL2 and MYC in vitro and in vivo at both the transcript and protein levels. Knock-down of SULT2B1b expression significantly suppressed tumor growth in nude mouse xenografts. Moreover, proliferation rates and SULT2B1b expression were highly correlated in the human hepatocarcinoma cell lines Huh-7, Hep3B, SMMC-7721 and BEL-7402 cells. Knock-down of SULT2B1b inhibited cell growth and cyclinB1 levels in human hepatocarcinoma cells and suppressed xenograft growth in vivo. In conclusion, SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC.
机译:羟基类固醇磺基转移酶2B1b(SULT2B1b)对向3β-羟基类固醇添加硫酸酯基具有很高的选择性。尽管以前的报道表明SULT2B1b与肝细胞的增殖有关,但SULT2B1b与肝癌细胞恶性表型之间的关系尚不清楚。在本研究中,我们发现人肝癌肿瘤组织中的SULT2B1相对高于其邻近组织。此外,通过CCK-8分析评估,SULT2B1b过表达促进小鼠肝癌细胞Hepa1-6的生长,而慢病毒介导的SULT2B1b干扰抑制生长。同样,抑制SULT2B1b的表达通过在体外和体内在转录本和蛋白质水平上调FAS的表达,下调cyclinB1,BCL2和MYC的表达,在Hepa1-6细胞中诱导细胞周期停滞和凋亡。抑制SULT2B1b表达可显着抑制裸鼠异种移植物中的肿瘤生长。此外,在人类肝癌细胞系Huh-7,Hep3B,SMMC-7721和BEL-7402细胞中,增殖速率和SULT2B1b表达高度相关。抑制SULT2B1b抑制人肝癌细胞中的细胞生长和cyclinB1水平,并抑制体内异种移植物的生长。总之,SULT2B1b的表达促进了肝癌细胞在体外和体内的增殖,这可能有助于肝癌的发展。

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