GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells

Abstract

Objective GP73 is a new hepatocellular carcinoma (HCC) marker, which is highly expressed in hepatocellular carcinoma and closely relates to prognosis. This study was to investigate the effects of GP73 on cellular proliferation, apoptosis, oxaliplatin (OXA) resistance and secretory clusterin (sCLU) of HCC cells.Materials and Methods Western blot and immunofluorescence was used to detect the expression of GP73 in 8 types of commonly used HCC cell lines. Drug resistance was induced by increasing concentration gradient method. The drug-resistant human HCC cell lines underwent GP73 overexpression or inhibition. Flow cytometry were used to detect the proliferation and apoptosis of HCC cell lines. The changes of sCLU were detected by enzyme-linked immunosorbent assay (ELISA).Results The expression of GP73 in MHC-97H cells was the highest and in Hep3B cells the lowest. The expression of GP73 was found further elevated in OXA-resistant MHC-97H cells. After the knockdown of GP73 in OXA-resistant 97H cells, the IC50 of OXA decreased and the ability of cell proliferation decreased significantly. After over-expression of GP73 in OXA-resistant Hep3B cells, the IC50 of OXA increased and the cell proliferation ability increased, showing that GP73 is critical for OXA resistant in HCC cell lines; No significant change of sCLU level in GP73 overexpressed Hep3B and GP73 blocked MHCC-97H were identified.Conclusion The expression level of GP73 is critical for the resistance of OXA in HCC cell lines.

TCF11 Has a Potent Tumor-Repressing Effect than Its Prototypic Nrf1α by Definition of both Similar yet Different Regulatory Profiles, with a Striking Disparity from Nrf2

“…As shown in Figure 8 ( A1-A12 ), a better OS was predicted to couple with increased expression of Nrf1, CHP2 ( calcineurin like EF-hand protein 2 ), CPS1 ( carbamoyl-phosphate synthase 1 ), FOXO1 ( forkhead box O1 ), IRS4 ( insulin receptor substrate 4 ) and/or NKX2-8 ( NK2 homeobox 8 ); this was also accompanied by reduced expression of AKR1B10 ( aldo-keto reductase family 1 member B10 ), EPO ( erythropoietin ), MUTYH ( mutY DNA glycosylase ) and/or PKM ( pyruvate kinase M1 /2). Besides, GP73 (also called GOLM1, golgi membrane protein 1) has been shown as a potential diagnostic marker for primary HCC [63,64], while GPC3 (glypican 3) acts as another key biomarker for early diagnosis of human HCC and a rational immunotherapeutic target for HCC [65,66].…”

High GP73 expression correlates with poor response to neoadjuvant chemotherapy and survival in gastric cancer

“…The mechanism of the correlation between GP73 expression and chemotherapy response in cancer is unclear. Ye et al reported that GP73 may signi cantly change cell proliferation and apoptosis so as to in uence the oxaplatin resistance in hepatic carcinoma cells [20]. Zhou et al's study found that GP73 induced cisplatin resistance in HT29 colon cancer cells was related to the activation of the mitogenactivated protein kinase/ERK and Wnt/β-catenin signaling pathways [21].…”

High GP73 Expression Correlates With Poor Response to Neoadjuvant Chemotherapy and Survival in Gastric Cancer: A Tissue Microarray Study

“…The mechanism of the correlation between GP73 expression and chemotherapy response in cancer remains to be determined. Ye et al reported that GP73 affect the oxaplatin resistance by involving in the cell proliferation and apoptosis process in HCC [20]. Zhou et al's study found that GP73 induced cisplatin resistance in HT29 colon cancer cells was related to the activation of the mitogen-activated protein kinase/ERK and Wnt/β-catenin signaling pathways [21].…”