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The Study Of Inhibitory Effect Of Somatostatin Analog Combined With Chemotherapeutic Drug On Human Gastric Cancer Cell Line

Posted on:2007-03-15Degree:MasterType:Thesis
Country:ChinaCandidate:H Y SuFull Text:PDF
GTID:2144360182491928Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Gastric cancer is one of the most common neoplasms and its incidence has increased rapidly in China. Chemotherapy is a main method used to treat gastric cancer, but the drugs have deficiency of low selectivity,severe toxicity and multi-drug-resistance. Somatostatin (SST) is a neuropeptide hormone binding to specific somatostatin receptors expressed in normal and neoplastic cells. Somatostatin analogs (SSTA) are able to inhibit gastric cancer with high selectivity and low toxicity. It is necessary to explore the effect of SSTA associated with chemotherapeutic drugs on the gastric cancer. ObjectiveTo find the better methods to treat gastric cancer, the effect of Somatostatin analogs (SSTA)-Octreotide (OCT) combined with chemotherapeutic drugs (mitomycin, MMC & Vincristine, VCR) on gastric cancer line were investigated.MethodsMTT colorimetric assay was used to evaluate the inhibitory effect of OCT,MMC, VCR and their combinations on proliferation of gastric cancer cell lines(SGC-7901) . Expression of p53 and bcl-2 related to apoptosis in gastric cancercell lines were detected by immunohistochemical method. Cell cycle of gastriccancer cell lines was detected by flow cytometry.Results1. Inhibition on gastric cancer cellOCT with concentration of 1 × 10-5g/L exerted the most significant inhibitory effect on gastric cancer cell line SGC-7901 as compared with the control group (P<0.05) and its rate of inhibition (IR) was 20.9%. The IR of OCT combinated with MMC (5 μg/ml) was 45.8%. The IR of OCT combinated with VCR (5 μg/ml) was 42.3%. The OCT combinated with MMC or VCR showed the significant stroger inhibiting effect on gastric cancer than that OCT, MMC(5 μ g/ml) or VCR(5 μg/ml) used singly . The inhibitory effect of OCT combinated with MMC is higher than that of OCT combinated with VCR (P>0.05) as the concentration of MMC and VCR were the same.2. Expression of p53 and Bcl-2 on gastric cancer cell lineThe index of positive cells expressing p53 in OCT, MMC, OCT+MMC, VCR and OCT+VCR were 20.4%, 8.9%, 9.03%, 24.8%, 30.8% (as compared with control group,P<0.05).The index of positive cells expressing Bcl-2 in OCT, MMC, OCT+MMC,VCR and OCT+VCR were 12.9%, 6.7%> 5%, 18.5%* 20.2%. The noteworthy difference was showed as compared with control group in MMC,OCT+MMC(PO.05) . 3. Cell cycle arrest on gastric cancer cellThe quantity percentage of cell treated by OCT staying in G2/M phase was higher than control group, but it did not show any noteworthy difference(P>0.05) . The percentage of cell treated by OCT+MMC staying in S phase was higher while percentage of cell staying in G0/G1 phase was lower. The percentage of cell treated by OCT+VCR staying in G2/M phase was higher while that staying in G0/G1 phase was lower. The noteworthy difference was showed as compared with control group (P<0.05) .ConclusionOCT inhibits proliferation on gastric cancer cell. The inhibitory effect of OCT combinated with MMC or VCR on gastric cancer cell was higher than that of MMC or VCR with same concentration. The expression of p53 is up-regulated and the expression of Bcl-2 is down-regulated by OCT as well as the percentage of cell staying in G2/M phase is arrested by direct and indirect mechanism. OCT combined with MMC can down-regulate the expression of Bcl-2 and decrease the down-regulation of expression of p53 induced by MMC used alone in gastric cancer cell, so that it induces S phase arrest. OCT combined with VCR can up-regulate the expression of p53 and induce G2/M phase arrest.
Keywords/Search Tags:Chemotherapeutic
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