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The Chemotherapy Sensitizing Effect Of131I-herceptin On Ovarian Cancer Cell SKOV-3

Posted on:2013-06-30Degree:MasterType:Thesis
Country:ChinaCandidate:P F JiangFull Text:PDF
GTID:2284330371473345Subject:Oncology
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Objective:ovarian cancer is the three malignant tumors in female reproductive system, although the pathogenesis is occupied only third, but its mortality rate ranks first in gynecological malignant tumors, five years survival rate of approximately30%[1], and the mortality rate has increased year by year. Ovarian cancer onset occult, lack of early symptoms, diagnosed with60%to70%of the patients had distant metastases. Current treatment modalities including operation, radiotherapy, chemotherapy, but due to the discovery of late, operation time has been lost, common chemotherapy, radiotherapy chemotherapy because of drug resistance and radiation resistance and other reasons, the limited efficacy of. Advanced ovarian cancer with intractable ascites, radiotherapy can effectively alleviate, repeated paracentesis is easy to cause electrolyte and acid-base balance disorders, and even the emergence of hypoalbuminemia, is one of the difficulties in treatment of advanced ovarian cancer. This experiment by immune targeted therapy methods, explore the high expression of Her-2types of ovarian cancer new treatment method. Observation of131I markers. Tuozhu monoclonal antibody (trastuzumab, trade name Herceptin) on Her-2expression in ovarian cancer cells SKOV-3chemotherapy sensitizing effect.Method:using Iodogen method to mark131I to Herceptin, and determination on chemical purity, radioactivity, immune binding rate, Herceptin rate of labeling, radioactivity for quality control, preparation of131I-herceptin. The blank group,131i-herceptin group, cisplatin (DDP) group,131i-herceptin and cisplatin (DDP) joint group. MTT method for the determination of different concentrations of cisplatin (DDP) and131i-herceptin and cisplatin (DDP) and131i-herceptin on SKOV-3growth inhibition rate, and draw the growth inhibition rate curve. Flow cytometry measurement of four groups with different treatment rate of apoptosis. Using immunohistochemi cal method were used to detect the untreated SKOV-3and131i-hercept in after48hours of SKOV-3Her-2and survivin expression, and compare the effects before and after the expression rate.Results:MTT measured by cisplatin (DDP) growth inhibition rate according to the growth inhibitory rate curves of4.685u g80%,3.760g70%,2.75g60%,2.320g50%,2.020g40%,1.560g as30%,1.130u g as20%. MTT measured by131I-Herceptin growth inhibition rate, according to the growth inhibitory rate curves of growth inhibition rate was10%when1311-Herceptin concentration was0.75×105Bq/ml. MTT measured by the combined group growth inhibition rate was significantly higher than that of additive group, P<0.05. Application of DDP’s formula groups interact with1311-Herceptin Q, the Q values were more than1. According to CDI (two drug interaction index) calculated the combined group CDI (two drug interaction index) were less than1. Flow cytometry measured SKOV-3cell apoptosis rate increased with the drug concentration decreases. The combined group of apoptosis rate was higher than that of single agent cisplatin (DDP) group and131I-Herceptin group, P<0.05. And the concentration of the combined group of apoptosis rate was obviously higher than the additive group, P<0.05.Group131I-Herceptin after treatment with Her-2labeling index from36%to21%, survivin gene marker index from21%to12%.Conclusion:1.1311-herceptin on ovarian cancer cell SKOV-3chemotherapy sensitizing effect.2. may:sensitization mechanism for downregulation of131I-Herceptin ovarian cancer cell SKOV-3Her-2and survivin gene expression.
Keywords/Search Tags:Herceptin, chemotherapy sensitizing, Her-2gene, survivin gene, 131I
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