PMID- 30317792 OWN - NLM STAT- MEDLINE DCOM- 20190329 LR - 20190329 IS - 1007-3418 (Print) IS - 1007-3418 (Linking) VI - 26 IP - 8 DP - 2018 Aug 20 TI - [Mechanism of angiotensin II (Ang II) on the proliferation of human hepatoma cell line HepG2 cells]. PG - 601-606 LID - 10.3760/cma.j.issn.1007-3418.2018.08.008 [doi] AB - Objective: To study the effect and mechanism of angiotensin (Ang II) on the proliferation of human hepatocellular carcinoma HepG2 cells. Methods: The effects of different concentrations of Ang II's (10(-8)-10(-4) mol/L) on proliferated hepatocellular carcinoma HepG2 cells were detected by CCK-8 assay. The expression of angiotensin II type 1 receptor (AT1) protein and activation of ERK1/2 protein in hepatocellular carcinoma HepG2 cells after processing with Ang II were assayed by Western blot. The cells were pretreated with candesartan (AT1 receptor antagonist), sorafenib (Raf kinase inhibitor) and PD98059 (ERK1/2 inhibitor) for 1.5 h and then Ang II (10(-6) mol/L) was added. CCK-8 assay was used to determine whether it could reverse the proliferation of Ang II, and ERK phosphorylation levels were detected by Western blot. The changes in Bcl-2 and c-myc gene expression before and after Ang II processing were detected by Rt-PCR. According to different data, t-test, one-way analysis of variance or SNK method were used for statistical analysis. Results: HepG2 cells treated with different concentrations of Ang II promoted cell proliferation after 24h and 48h. After 24 h, cell vitality was strongest with Ang II concentration 10(-5) mol/L and the absorbance value was 0.990 8+/-0.097 8; and again after 48 h, the cell viability was strongest with Ang II concentration 10(-6) mol/L and the absorbance value was 1.302 7 +/- 0.030 9. Moreover, the pro-proliferation effect of Ang II on HepG2 cells blocked candesartan, sorafenib and ERK1/2 isolated inhibitors. After treatment with 10(-6) mol/L Ang II, Western blot showed that Ang II significantly promoted AT1 receptor expression and phosphorylation of ERK1/2 protein confirmed that Ang II activated the AT1/RAF/ERK1/2 signaling pathway. In addition, Rt-PCR detection showed that the downstream of Bcl-2 and c-myc genes expressions rose significantly when the concentration of Ang II ranged from 10(-8) to 10(-6) mol/L. Conclusion: Ang II can promote the proliferation of HepG2 cells by activating AT1/Raf /ERK1/2 signaling pathway and enhance the downstream of Bcl-2 and c-myc gene expression. FAU - Qi, R AU - Qi R AD - Youyi Hospital, Dalian Medical University, Dalian 116000, China. FAU - Lei, C G AU - Lei CG AD - Department of Hepabilary Surgery, Qingdao Muliciple Hosptisal, Qingdao 266071, China. FAU - Bai, Y X AU - Bai YX AD - Xinhua Hospital, Dalian Medical University, Dalian 116000, China. FAU - Xing, X AU - Xing X AD - Department of Hepabilary Surgery, Qingdao Muliciple Hosptisal, Qingdao 266071, China. LA - chi PT - Journal Article PL - China TA - Zhonghua Gan Zang Bing Za Zhi JT - Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology JID - 9710009 RN - 11128-99-7 (Angiotensin II) SB - IM MH - Angiotensin II/*pharmacology MH - Carcinoma, Hepatocellular MH - Cell Line MH - Cell Proliferation/*drug effects MH - Cells, Cultured MH - Genes, bcl-2/*drug effects/genetics MH - Genes, myc/*drug effects/genetics MH - Hep G2 Cells/*drug effects MH - Humans MH - Liver Neoplasms MH - Reverse Transcriptase Polymerase Chain Reaction OTO - NOTNLM OT - Angiotensin II OT - Angiotensin type 1 receptor OT - Carcinoma, hepatocellular OT - Extrallular signal-regulated kinase 1/2 OT - Raf EDAT- 2018/10/16 06:00 MHDA- 2019/03/30 06:00 CRDT- 2018/10/15 06:00 PHST- 2018/10/15 06:00 [entrez] PHST- 2018/10/16 06:00 [pubmed] PHST- 2019/03/30 06:00 [medline] AID - 10.3760/cma.j.issn.1007-3418.2018.08.008 [doi] PST - ppublish SO - Zhonghua Gan Zang Bing Za Zhi. 2018 Aug 20;26(8):601-606. doi: 10.3760/cma.j.issn.1007-3418.2018.08.008.