| Survivin , a new member of IAP family, can inhibit apoptosis by combining with Caspase3 and Caspase7. Sufficient data show that survivin plays an important role in apoptosis pathway and that its' expression is highly related with cancer and associated with an unfavorable prognosis. Some study indicated that survivin may be a promising target of anticancer therapy. Taxol is a compound extracted from Yew and clinical data has proved that taxol is a promising drug for the chemotherapy of gastrointestinal cancer. Inducing apoptosis is an important antitumor mechanism of Taxol, hence Taxol may have an influence on the expression of survivin. Studying the role of survivin in Taxol's effects will contribute to clarify the antitumor mechanism of Taxol. With the transfection mediated by Lipofect Amine, we studied effects of survivin antisense and it's combination with Taxol on the development of experimental gastric cancer in order to evaluate the effect of survivin targeted gene therapy in vivo.Part 1: The expression of survivin in gastric carcinoma, and it's relationship with the expression of p53 and c-erbB2 Objective: To study the expression of survivin in gastric carcinomas and its relationship with the expression of p53, c-erbB2.Method: Using immunohistochemical staining method, we examined the expression of survivin, p53 and c-erbB2 genes in 20 cases of chronic gastritis and 56 cases of gastric carcinomas.Results: Survivin expressed in 27 of 56(48.2%) cases of gastric carcinoma tissues and 1 of 20(5%) cases of chronic gastritis. Over expression of survivin had no relation with age, tumor depth, tumor size, and disease stage, but was significantly related to histological type. The expression of survivin significantly segregated with intestinal type cases as compared with diffuse type cases. Survivin positive cases were significantly associated with p53 expression(15/22,68.2% versus 12/34,35.3%,P<0.05) and c-erbB2 expression(16/20,80% versus 11/36,30.6%,P<0.01).Conclusions: These data indicated that survivin play a important role in the onset of gastric cacinoma and suggested potential correlation between survivin and c-erbB2, and between survivin and p53 as well.Part2: Regulation on survivin expression in gastric cancer cells by Taxol and it's mechanismObjective: To study the regulation of Taxol on the expression of survivin in gastric cancer cells and it's mechanism. Method: Survivin expression of five gastric cancer cell lines were examined by western blot, and the IC50 of Taxol to each cell line was detected by MTT. We also examined survivin expression of each cell line after treated with 60ng/ml Taxol in 24 hours, and examined survivin expression in BGC-823 cell line after treat with 600ng/ml Taxol in 72 hours. The expression of JNK kinase, phosphorylation of JNK kinase and phosphorylation of p38 kinase were detected simultaneously. In addition, SB203580 and curcumin were used to inhibit p38 and JNK pathway respectively before treatment with Taxol for 72 hours, then survivin expression were examined by western blot, and cell apoptosis were detected by TUNEL and 89kDa-PARP. Result: The IC50 of Taxol to these five gastric cell lines were correlated with survivin expression. Survivin expression of these five cell lines increased to some extend respectively during the 24 hours after 60ng/ml Taxol treatment. When BGC-823 cells were treated with 600ng/ml Taxol, the expression of survivin increased 7 fold at 24 hour and then decreased. JNK kinase expression increased after Taxol treatment and remain at a high level for about 48 hours, and phosphorylation of p38 kinase increased from 1 to 3 hour after Taxol treatment. Pretreated BGC-823 with curcumin 10uM for 1 hour before Taxol treatment, survivin expression increased 1.3 time in 24 hour, the peak of 89kDa-PARP delayed, and apoptosis index examined by TUNEL decreased. When pretreated with SB203580 10uM for 1 hour, no increase of survivin expression was detected during 24 hour, the presence of 89kDa-PARP was brought forward,...
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