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Ubiquitin-proteasome pathway (UPP) is the major system for the selective degradation of cellular proteins that play key roles in cellular processes. Previous study indicated that ubiquitin-proteasome inhibitor MG-132 could inhibit growth of some carcinoma. However, anti-carcinoma mechanism of MG-132 is unclear. Our objective was to investigate mechanisms of growth inhibitory effect of MG-132 on gastric carcinoma cells. Gastric carcinoma cell SGC-7901 was treated with ubiquitin-proteasome inhibitor MG-132. Cell growth suppression was evaluated with 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. DNA synthesis was evaluated by 3H-thymidine (3H-TdR) incorporation. Activity of telomerase was examined by telomeric repeat amplification protocol (TRAP) PCR-ELISA. Cell cycle and apoptosis were detected by flow cytometry (FCM). DNA fragment analysis was used to confirm the presence of apoptosis. Expression of p27kip1 and survivin was detected using the western blot method. After exposed to MG-132, the growth and value of 3H-TdR incorporation of gastric carcinoma cells were obviously inhibited. TRAP PCR-ELISA showed that light absorption of cells gradually decreased after exposed to 5 μ M of MG-132 for 24, 48, 72 and 96 h (P < 0.01). The percentage of cells at G0/G1 phase was increased and that at S and G2/M phase was decreased (P < 0.01). The ratio of apoptotic cells treated with 5 μ M MG-132 for 96 h was 53.7 ± 6.4%. Agarose electrophoresis showed marked ladders. Moreover, expression of p27kip1 of cells was increased and expression of survivin was decreased. Our results suggest that MG-132 inhibits telomerase activity, induces apoptosis and G1 arrest which is associated with upregulated p27kip1 expression and downregulated survivin expression in gastric carcinoma cells. [ABSTRACT FROM AUTHOR]

Previous study indicated that p27kip1 gene transfer can obviously inhibit the growth of some carcinoma cells. The purpose of this study was to investigate anticarcinoma mechanism of p27kip1. Gastric carcinoma cell strain SGC-7901 was transfected with recombinant adenovirus vector carrying human p27kip1 gene (Ad-p27kip1). Expression of survivin was detected using the western blot method and activity of telomerase was examined by telomeric repeat amplification protocol (TRAP) PCR-ELISA in gastric carcinoma cells. Our results suggest that upregulated p27kip1 can downregulate survivin expression and inhibit telomerase activity in gastric carcinoma cells. [ABSTRACT FROM AUTHOR]