Abstract
Backgrounds and Objective: Proteasome inhibitors are a kind of novel anti-tumor agent which can inhibit cell growth and induce apoptosis by inhibiting the function of proteasome system and impacting the degradation of proteins related to cell growth or apoptosis. The aim of the study is to explore the effect of proteasome inhibitor Z-Leu-Leu-Phe-CHO (ZLLFC) singly or combined with cisplatin on proliferation or apoptosis of humnan gastric cancer cell SGC-7901, as well as its influence on the expression level of excision repair cross complementing 1(ERCC1) mRNA. Methods: MTT assay was used to calculate the growth inhibitory rate of human gastric cancer cell SGC- 7901. The apoptotic cell morphology was observed with electron microscopy, the apoptotic rate was analyzed by flow cytometry and by expression level of ERCC1 mRNA detected by RT-PCR. Results: Proteasome inhibitor ZLLFC could inhibit the growth of gastric cancer cell SGC-7901. Combined application of proteasome inhibitor ZLLFC and cisplatin significantly increase the inhibitory effect on SGC-7901 cells, induced apoptosis and increased the apoptotic rate. While, the expression level of ERCC-1 mRNA in SGC-7901 cells in the combined group was significantly lower than that of the cisplatin group (p
Highlights
The highly conserved ubiquitin–proteasome system is the principal machinery for extralysosomal protein degradation in eukaryotic cells
The objective of the present study is to explore the effect of proteasome inhibitor Z-Leu-Leu-Phe-CHO (ZLLFC) singly or combined with cisplatin on the proliferation or apoptosis of humnan gastric cancer cell SGC-7901, as well as its influence on the expression level of excision repair cross complementing 1(ERCC1) mRNA
Proteasome inhibitors are a kind of novel anti-tumor agent which can inhibit cell growth and induce apoptosis by inhibiting the function of proteasome system, impacting the degradation of proteins related to cell growth or apoptosis
Summary
The highly conserved ubiquitin–proteasome system is the principal machinery for extralysosomal protein degradation in eukaryotic cells. The 26S proteasome, a large multi-catalytic multi-subunit protease that processes cell proteins by limited and controlled proteolysis, constitutes the central proteolytic component of the ubiquitin– proteasome system. Given that ubiquitin-proteasome pathway affects multiple cellular process, its inhibition by proteasome inhibitor affects a broader spectrum of proteins with diverse functions. Proteasome inhibitors block protein degradation and cause accumulation of misfolded or damaged proteins, which in turn triggers heat shock response and cell death [2,3]. Inhibition of the ubiquitin proteasome pathway (UPP) leads to significant buildup of cytotoxic proteins and activation of apoptotic pathways, in rapidly proliferating cells. Proteasome inhibitor induces the accumulation of pro-apoptotic proteins in tumorigenic cells but not in the normal tissue [4]
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