Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2

作者：Huang Bee Piao; Lin Chun Shiang; Wang Chau Jong; Kao Shao Hsuan

来源：International Journal of Medical Sciences, 2017, 14(3): 284-293.

DOI：10.7150/ijms.17861

• Hepatocellular carcinoma
• Tumor necrosis factor-alpha
• apoptosis
• Label-free proteomic analysis

Tumor necrosis factor alpha (TNF alpha) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNF alpha on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNF alpha stimulus. We observed that HepG2 cell revealed a higher resistance to TNF alpha-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By using a label-free quantitative proteomic analysis, we found that 520 proteins were differentially expressed in the HepG2 cells exposed to TNF alpha, including 211 up-regulated and 309 down-regulated proteins. We further confirmed several proteins with significant expression change (TNF alpha/control ratio>2.0 or < 0.5) by immunoblotting using specific antibodies. We also analyzed the differential expressed proteins using Gene ontology and KEGG annotations, and the results implicated that TNF alpha might regulate ribosome, spliceosome, antigen processing and presentation, and energy metabolism in HepG2 cells. Moreover, we demonstrated that upregulation of heat shock protein 70 (HSP70) was involved in both the promoted migration and the inhibited apoptosis of HepG2 cells in response to TNF alpha. Collectively, these findings indicate that TNF alpha alters protein expression such as HSP70, which triggering specific molecular processes and signaling cascades that promote migration and inhibit apoptosis of HepG2 cells.

• 出版日期2017