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Effect Of Combined Therapy With PI-3K Inhibitor LY294002 And Paclitaxel In In Vivo Ovarian Cancer Model

Posted on:2005-05-02Degree:MasterType:Thesis
Country:ChinaCandidate:X N WangFull Text:PDF
GTID:2144360122995961Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Malignant tumor is a sort of disease that drastically threatens human health and life. Among gynecological carcinoma, ovarian carcinoma the highest fatality rate. During the last decades, with the development of the cytoreductive surgery and chemotherapy , the survival rate of ovarian carcinoma has been enhanced. However, the prognosis that remains poor due to the lack of effective early diagnostic and therapeutic methods. Paclitaxel,which called a natural product that isolated from Taxus brevifolia It has been significant anti-tumor activity in several human tumors, particularly in advanced ovarian and breast carcinomas, and FDA has been already permitted it for second-line treatment of them, by the result of clinical test in America . But the drug resistance and side effects of Paclitaxel limit its clinical appliance as well as other medicine for chemotherapy. Therefore, it is necessary that we should explore scheme of diagnosis and treatment. Phosphoinositide-3kinase(PI-3K)is a lipidic we called secondary messenger that interferes the transduction of signal in cell. The activation of the signal transduction pathway can promote cell cycle and inhibit apoptosis. A number of research suggested that PI-3K plays an important role in the pathogeny developments, invasion and metastasis of ovarian carcinoma. It is proved that 2-(4-morpholinyl)-8-phenyl chromone(LY294002) completely and specificallyinhibit from the activity of PI-3K. In this study shows that we are planting HO-8910PM in order to construct an ovarian carcinoma sample, we can put a cell line of ovarian carcinoma into subcutis of nude mouse. Therefore , we can freely divide them into four groups and treat them with LY294002 and Paclitaxel,which single and combination, on the control of ovarian tumor growth to evaluate whether combined therapy with Paclitaxel and LY294002 would result in increased efficacy .Methods: 40 nude mice were freely divided into 4 groups: negative control group(normal nude mice) ,positive control group(nude mice that are ovarian carcinoma model) Paclitaxel treated group(ovarian carcinoma model that treated with Paclitaxel) and combination treated group(ovarian carcinoma model that treated with Paclitaxel and LY294002 ). After ten days, the inoculation of HO-8910PM into the other three groups to form tumors except for negative control group ,the positive control group was treated with saline ; Paclitaxel treated group was treated with 20mg/kg of Paclitaxel and combination treated group was treated with 20mg/kg of Paclitaxel and 100mg/kg LY294002 every others day. The weight of body and diameter of tumor were measured everyday. After seven days treatment, firstly, we executed the nude mice that obtain blood from them treated with heparin and blood analysis; secondly, we detached the tumors completely and calculated the inhibition rate of tumor growth by weighing the tumors; thirdly, we assay the content of malondial dehyde (MDA) and superoxide dismutase (SOD) in livers of the nude mice; at last, we got pathological sections of the tumors ,we can find stained by hematoxylin-esoin(HE), we were analyses by immunohistochemistry that light microscopy and electron microscopy, we will evaluate whether therapycombined with Paclitaxel and LY294002 would result in increased efficacy for the ovarian carcinoma model .Results: (1 )The tumor growth of ovarian carcinoma model after different treatment: tumors of the two control groups has a rising line, he tumor growth of those treated with drugs was inhibited from while compare with treated group was inhibited obviously combined with Paclitaxel treated group.(2) The inhibition rate of tumor growth: that the combination treated group was 47.78% while that of the Paclitaxel treated group was 24.18%. (3) The assay of ccomparation in tent of malondialdehyde (MDA) and superoxide dismutase (SOD) in livers of the nude mice: MDA is the product of oxidative damage in organism and the higher content of it implies heavier injury; the content of it in the positive control group was higher than the nega...
Keywords/Search Tags:PI-3K, Paclitaxel, LY294002, ovarian carcinoma, tumor therapy
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