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IFN-α And KLT Induced Apoptosis And Inhibited Lymphangiogenesis In Gastric Cancer Cells

Posted on:2011-10-19Degree:MasterType:Thesis
Country:ChinaCandidate:T LiFull Text:PDF
GTID:2144360305952605Subject:Gastrointestinal gland surgery
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Objective:Gastric cancer is one of the digestive tract cancer, Lymph node metastasis is the main reason to cause gastric cancer patients'treatment failure and death. At the time of diagnosis approximately 60% in the resectability of gastric cancer has occurred lymph node metastasis,result of advanced gastric cancer patients after surgery the overall five-year survival rate was only about 40%[1]. This study is based on the model that the human gastric carcinoma transplanted subcutaneously in nude mice ,mainly detected by immunohistoche- mistry in gastric cancer cells in nude mice apoptosis, VEGF-C expression and the adjacent area lymphangioge-nesis, designed to filter out new drugs that can effectively induced apoptosis and inhibited the nude subcutaneous tumor lymphangiogenesis, for the clinical inhibition of gastric cancer and other malignant tumors of Lymphangiogenesis, blocking lymphatic metastasis ways to improve patient survival rate to provide experimental basis.Method:1. Cultured gastric cancer cells SGC-7901. 2. Subcutaneous inoculation method used to establish human gastric cancer xenografts in nude mice.3. Nude group and administration: the nude mice were randomly divided into six groups, namely: positive control group (5-FU), negative control group (NS), IFN-αlow-dose group, IFN-αhigh-dose group,KLT low-dose group, KLT high-dose group.Started on the same day administration, continuous administra- tion for 7 days.4. Death nude, stripping tumor tissue, weigh and calculate the tumor inhibition rate of tumor weight.5. TUNEL assay of apoptosis in tumor tissue of tumor cells.6. Immunohistochemical detection of VEGF-C expression in cancer cells, lymphatic endothelial marker D2-40 lymphatic endothelial cell markers measured tumor micro-vessel density (LVD).Results:1. INF-αand KLT on gastric cancer growth inhibitionAfter the drug 5-FU group, INF-αlow and high dose group and KLT low and high dose group significantly slowed tumor growth, tumor weight was significantly lower than NS group, the inhibition rates were 29.30%, 18.48%, 24.67%, 21.15%, 30.96%, compared with the NS group differences were statistically significant (p<0.05).2. INF-αand KLT in gastric cancer cell apoptosisTUNEL test results showed that tumor cells in nude mice in each group apoptosis index (AI,%), respectively: NS group was 6.39±1.34; 5-FU group was 29.5±3.27; INF-αlow-dose group was 15.39±3.09; INF-αhigh-dose group was 25.53±4.38; KLT low-dose group of was 13.29±3.37; KLT high-dose group was 16.14±4.21. INF-αlow and high dose group, KLT low and high dose group ,5-FU group, three groups of the AI values increased significantly compared with NS group ( p<0.05); the same time, 5-FU group, INF-αhigh-dose group than in INF -αlow-dose group, KLT low-dose, KLT high-dose group AI significantly increased (p<0.05).3. INF-αand KLTon gastric cancer tissue expression of VEGF-CImmunohistochemistry test results of the optical density value of each group: NS group was 0.736±0.082; 5-FU group was 0.714±0.079; INF-αlow-dose was group 0.323±0.058; INF-αhigh-dose group was 0.285±0.055; KLT low-dose group was 0.672±0.063; KLT high-dose group was 0.391±0.060. INF-αlow-dose group, INF-αhigh-dose group and KLT high-dose group tumor expression of VEGF-C were lower than the average of each group on the NS group, and the difference was statistically significant (p<0.05).4. INF-αand KLT on gastric cancer tissue LVDImmunohistochemistry results in each group micro-vessel density LVD values: NS group was 16.75±5.23; 5-FU group was 15.23±5.18; INF-αlow-dose group was 13.22±3.48; INF-αhigh-dose group was 11.37±2.39; KLT Low-dose group was 15.12±4.95; KLT high-dose group was 13.14±3.82. INF-αlow-dose group, INF-αhigh-dose group and high-dose group KLT tumor of LVD is less than the control group NS group LVD values, and the difference was statistically significant (p<0.05).Conclusion:1. High-dose and low-dose interferon-αcan effectively inhibit the growth of tumors transplanted subcutaneously into nude mice,promote tumor cell apoptosis and inhibit tumor cell VEGF-C expression, inhibit new lymphatic vessels around the tumor. The high-dose interferon-αwas more effectively than the low-dose interferon-α. 2. High-dose and low-dose KLT can inhibit tumor growth in nude mice transplanted subcutaneously,promote tumor cell apoptosis, high-dose KLT injection can effectively inhibit tumor cell VEGF-C expression, inhibit new lymphatic vessels around the tumor, while the low-dose KLT did not show the inhibition of tumor lymphatic vessels surrounding the new role.3. 5-FU can inhibit the growth of subcutaneous tumors, promoting tumor cell apoptosis. 5-FU showed no inhibition of tumor cell VEGF-C expression and inhibit the formation of lymphatic vessels around the tumor. But Mice appeared heavy toxicity.
Keywords/Search Tags:Gastric Carcinoma, lymphangiogenesis, lymph node metastasis, VEGF-C
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