Experimental Study of Rhein Inhibits the Invasion and Migration of HepG2 Cells by ERK Signaling Pathway

Keywords

HepG2 cells
Rhein
ERK pathway
Cell invasion
Cell migration

How to Cite

Wang, Y., Liu, L. ., Li, N., Zhou, J. ., & Du, L. . (2021). Experimental Study of Rhein Inhibits the Invasion and Migration of HepG2 Cells by ERK Signaling Pathway. Iranian Red Crescent Medical Journal, 23(11). Retrieved from https://ircmj.org/index.php/IRCMJ/article/view/1310

Abstract

Objective: To investigate the effectiveness of Rhein on the proliferation, invasion and migration of human hepatoma cell line HepG2 and its possible mechanism.Methods: Human hepatoma cell line HepG2 was treated with different concentrations of Rhein (Rhein treatment group) and culture in culture medium alone (control group).The proliferation activity of the cells was determined by methyl Thiazolyl Tetrazolium (MTT) colorimetry.Transwell assay detected the invasion and migration of cells in each group.Cell scratch test was used to detect the migration ability of cells in each group.Excella-phospho-excellar signal-regulated kinase (P-ERK) activity was determined by ELISA after treatment with 50μ mol/L Rhein at different times.Western blot was used to detect ERK protein expression in HepG2 cells treated with 50 μmol/L Rhein.Results: Compared with the control group, the proliferation activity, invasion and migration ability of HepG2 cells in the Rhein treatment group were all decreased (P< 0.05), and the p-ERK relative activity of HepG2 cells treated with Rhein was decreased (P < 0.05).Conclusion: Rhein inhibits the invasion and migration of HCC cells, possibly by inhibiting the ERK pathway.

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108. doi: 10.3322/caac.21262. PMID: 25651787.
  2. Chen W,  Zheng RS,  Baade PD,  Zhang SW, Zeng HM,  Bray F. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115-32. doi: 10.3322/caac.21338. PMID: 26808342
  3. Shen J, He LY, Li C, Wen TF, Chen WX, Lu CL, et al. Nomograms to predict the individual survival of patients with solitary hepatocellularcarcinoma after hepatectomy. Gut Liver. 2017;11(5):684-92. doi: 10.5009/gnl16465. PMID: 28651303.
  4. Lee J, Lee JH, Yoon HB, Lee HJ, Jeon H, Nam J. Extraordinary radiation super sensitivity accompanying with sorafenib combination therapy: what lies beneath?. Radiat Oncol J. 2017;35(2):185-8. doi: 10.3857/roj.2017.00262. PMID: 28712281.
  5. Hsiao JH, Tsai CC, Liang TJ, Chiang CL, Liang HL, Chen IS, et al. Adjuvant hepatic arterial infusion chemotherapy is beneficial for selective patients with hepatocellular carcinoma undergoing surgical treatment. Int J Surg. 2017;(45):35-41. doi: 10.1016/j.ijsu.2017.07.071.
  6. Hao Sun, Luo GW, Chen DH, Xiang Z. Acomprehensive and system review for the pharmacological mechanism of action of rhein, an active anthraquinone ingredient. Front Pharmacol. 2016;17(7): 247.  doi: 10.3389/fphar.2016.00247.PMID: 27582705.
  7. Bi FF, Chen F, Li YN, Wei A, Cao WS. Klotho preservation by Rhein promotes toll-like receptor 4 proteolysis and attenuates lipopolysaccharide induced acute kidney injury. J Mol Med. (Berl.) 2018; 96(9):915-927. doi: 10.1007/s00109-018-1644-7. PMID: 29730698.
  8. Lee S, Han S, Park JS, Jeong AL, YangY. Herb mixture C5E aggravates doxorubicin-induced apoptosis of human breast Cancer cell lines. J Kor Soc Appl Biol Chem. 2013;56(5): 567-573. doi:10.1007/s13765-013-3195-5.
  9. Cho YR, Kim JK, Kim JH, Oh JS, Seo DW. Ligularia fischeri regulates lung cancer cell proliferation and migration through down-regulation of epidermal growth factor receptor and integrinbeta1expression. GenesGenomics. 2013;35(6):741-746. doi:10.1007/s13258-013-0124-2.
  10. Entidhar Al Sawah, Marchion DC, Xiong Y, Ramirez IJ, Abbasi F, Boac BM, et al.The Chinese herb polyphyllin D sensitizes ovarian cancer cells to cisplatin-induced growth arrest. J Cancer Res Clin Oncol. 2015;141(2):237-42. doi: 10.1007/s00432-014-1797-x.
  11. ChangSJ, Huang SH, Lin YJ, Tsou YY, Lin CW. Antiviralactivity of Rheum palmatum methanol extract and chrysophanol againstJapanese encephalitis virus. Arch. Pharm. Res. 2014;37:1117–1123. doi: 10.1007/s12272-013-0325-x.
  12. ZhouYX, Xia W, Yue W, Peng C, Rahman K, Zhang H, et al. Rhein:a review of pharmacological activities. Evid Based Complement Alternat Med. 2015;578107. doi: 10.1155/2015/578107.
  13. Tamura T, Yokoyama T, Ohmori K. Effects of diacerein on indomethacin-induced gastric ulceration. Pharmacology. 2001;63:228. doi: 10.1159/000056138. PMID: 11729361.
  14. Li XH, Li M, Tao YR. Development of pharmacological effects of rhein and its derivatives. Modern medicine and clinic. 2010;25:417. doi:10.7501/j.issn.1674-5515.
  15. Li Y, Xu Y, Lei B, Wang W, Ge X, Li J, et al. Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway. Braz J Med Biol Res.        2012;45(11):1052-9.  doi: 10.1590/s0100-879x2012007500125.
  16. Blacher E, Ben Baruch B, Levy A, Geva N, Green KD, Garneau-Tsodikova S, Fridman M, Stein R, et al. Inhibition of glioma progression by a newly discovered CD38 inhibitor. Int J Cancer. 2015;136(6):1422-33. doi: 10.1002/ijc.29095. PMID: 25053177.
  17. Huang HJ, Lin CC, Chou HC, Chen YW, Lin ST, Lin YC, Lin DY, Lyu KW, Chan HL, et al. Proteomic analysis of rhein-induced cyt: ER stress mediates cell death in breast cancer cells. Mol Biosyst. 2014;10(12):3086-100. doi: 10.1039/c4mb00451e.
  18. Chen YY, Chiang SY, Lin JG, Ma YS, Liao CL, Weng SW, Lai TY, Chung JG, et al. Emodin, aloe-emodin and rhein inhibit migration and invasion in human tongue cancer SCC-4 cells through the inhibition of gene expression of matrix metalloproteinase-9. Int J Oncol. 2010;36(5):1113-20. doi: 10.3892/ijo_00000593.
  19. Ip SW, Weng YS, Lin SY, Mei-Dueyang, Tang NY, Su CC, Chung JG, et al. The role of Ca+2 on rhein-induced apoptosis in human cervical cancer Ca Ski cells. Anticancer Res. 2007;27(1A):379-89. PMID: 17352257. PMID: 17352257.
  20. Shi P, Huang Z, Chen G. Rhein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma BEL-7402 cells. Am J Chin Med. 2008;36(4):805-13. doi: 10.1142/S0192415X08006259. PMID: 18711776.