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The Imaging Observation Of The Inhibitory Effects Of Weianning Mixture On Orthotopic Transplantation Tumor Model Of Human Gastric Cancer And The Study Of Its Molecular Mechanism

Posted on:2011-09-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:J W LuFull Text:PDF
GTID:1114360308472405Subject:Traditional Chinese Medicine
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Objective:To study inhibitory effects and toxicity of Jianpihuoxue antidotarium (Weianning Mixture) on Human gastric cancer in a fluorescent orthotopic gastric tumor model in nude mice.To study the effect of Jianpihuoxue antidotarium on COX-2 expression, telomerase activity and cell apoptosis of gastric cancer cell in order to elucidate its inhibitory mechanisms.Method:NUGC-4 human gastric cancer cell line was tranfected with red fluorescent protein retroviral vector pLNCX-DsRed-2.Orthotopic gastric tumor model was established by implanting tumor tissue fragments on the gastric of nude mouse.The tumor-bearing mice were randomly grouped into four groups each comprising 8 mice (Groupl, untreated control; Group 2,5-FU positive control; Group 3:high dose of Weianning; Group 4:low dose of Weianning). The treatments were initiated on day 7 after tumor implantation. Tumor size was measured by fluorescence in vivo imaging on day 7,14,21 and 28.The study was terminated and open fluorescence imaging was performed on day 35 to examine primary tumor and metastasis. The primary tumor was excised and weighed at autopsy.The tumor tissue was collected and analyzed for COX-2 protein expression, telomerase activity and cell apoptosis by immunohistochemistry and TUNEL method.Result:Significant differences of the tumor volume could be seen in the 5-FU and the high dose Weianning treated groups by comparison to the untreated group on day 14 (p=0.0146,0.0080) and day 28 (p=0.0035,0.0001) after treatment initiation. However, no significances differences could be seen between the low doses Weianning treated groups and the untreated group at any time point. Significant differences of the tumor weight at autopsy could be seen in the 5-FU and the high dose Weianning treated groups by comparison to the untreated group (p=0.012, 0.016).No significances differences of the tumor weight could be seen between the low dose Weianning treated groups and the untreated group. Lower incidence of lymph node, spleen, liver and total metastases were found in the 5-FU and the high dose Weianning treated groups by comparison to the untreated group, but no statistical significance. No difference of metastasis incidence was found between the low doses Weianning treated group and the untreated group. The body weight did not show a significant drop in all treated groups during 4 weeks of the experiment, indicating no apparent toxicity for high and low dose treatment of Weianning.Significant higher COX-2 protein expression (87.5%) was detected in the untreated group by comparison to the high and low dose Weianning groups (25.0%) (p=0.041).No significant difference for COX-2 protein expression was found between the 5-FU treated group and the untreated group although lower COX-2 expression level (62.5%) was detected in the 5-FU treated group (p=0.569).Significant lower telomerase expression (12.5%) was detected in the high dose Weianning group by comparison to the untreated group (100.0%) (p=0.001) and 5-FU treated groups (87.5%) (p=0.01).Lower telomerase expression (50.0%) was detected in the low dose Weianning group, but no significant difference (p=0.077).Significant higher cell apoptosis (0.64±0,05%) was detected in the high dose Weianning group by comparison to the untreated group (0.53±0.09%, p=0.007) and 5-FU treated groups (0.50±0.09%, p=0.001).No difference of cell apoptosis was found between the low dose Weianning treated group (0.52±0.05%) and the untreated group (p=0.742).Conclusion:High dose Weianning showed significant efficacy on the tumor growth and non-significant inhibitory effect on metastasis of NUGC-4 gastric cancer in orthotopic tumor mouse model without obvious toxicity. The inhibitory effect is dose-dependent. Weianning can reduce COX-2 protein expression and telomerase activity and induce apoptosis in gastric cancer cell, which is probably one of mechanisms against cancer.
Keywords/Search Tags:Gastric cancer, Nude mice, Molecular imaging, Jianpihuoxue antidotarium, Cyclooxygenase-2 protein expression, Telomerase activity, Apoptosis
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