Biologic Characteristics Of Intraperitoneal Transplantation Model Of Human Ovarian Carcinoma In SCID Mice And Antiangiogenesis Of Ginsenoside Rg3

Background0varian carcinoma has the highest morta1ity in a11gyneco1ogica1 cancer for 1acking an effective diagnosis. A1thoughvarious techniques of management deve1oped, the prognosis has notbeen improved. It is imperative to exp1ore new ways of diagnosisand treatment. For recent years, antiangiogenesis has been be1ievedas a new way of treatment with the progress of angiogenesis study.In 197l, Fo1kman reported the growth and metastatic spread ofsolid tumors to be dependent on angiogenesis. The nutrition supportfrom tumor vessle is essentia1 for the growth of tumors. That is, byblocking angiogenesis of tumors and nutritiona1 support, tumorce11s wou1d die for ischemia and hypoxia. Many researches haveindicated that inhibiting tumor angiogenesis are ab1e to restraingrowth and metastasis of tumors. So far, more than 20 kinds ofangiogenesis inbibitors have been found, which were ab1e to b1ockthe vascu1arization in various pathways. Ginsenoside Rg3 isconsidered as one of those agents, which give p1ay to anti-neop1ast ic activi ty by suppressing tumor angiogensis. However,most of studies on1y described morpho1ogical changes, theirdetai1ed antiangiogenesis mechanism was not reported.To study angiogenesis and antiangiogenesis of ovariancarcinoma, an optimal mode1 providing a better understanding ofits biologica1 behavior and deve1opment of new therapeuticstrategies is needed. Because of defecting both ce11u1ar andhumora1 immunity, severe combined immunodeficiency (SCID) mouse canaccept and maintain xenogeneic tissue, organ or tumor. Therefore itis regarded as a more advanced anima1 mode1 than nude mouse.A1though SCID mouse with subcutaneous xenograft of ovariancarcinoma has been estab1ished success fu1ly, it can not simu1atethe formation of ascite and intraperitonea1 metastasis, so thatits app1ication in research was restricted. As we know there is nodomestic report about transp1antation of human ovarian carcinomainto peritonea1 cavity of SCID mouse, and further report relatingto antiangiogenesis based on this mode1.I. Bio1ogical characteristics of model of himan ovarian carcinomain SCID mouse. 0bjective:To deve1op a human ovarian carcinoma SK0V3mode1 in SCID mouse and research its bio1ogic characteristics inorder to provide an adequate experimental animal model for theovarian carcinoma research in vivo. Methods: Concentration of lxl07human ovarian carcinoma SK0V3 ce1ls was injected intraPeritoneallyinto fema1e SCID mouse, which was raised in SPF environment. Thetumor growth was observed. Results: 1. Tumor formed with bloodyascites in all of SCID mice. 2. Metastasis formed main1y indiaphragn, mesentery, peritoneum and around 1iver, which wasconfirmed by histopathology. 3. Features of primary cu1ture ofce11s transp1anted kept as saJne in morpho1ogy, growth and secretingCA125 as that of ovarian carcinoma ce1l line SK0V3.II. Study on antiangiogenesis of Rg3. 0bjective: To investigatethe antiangiogenesis of ginsenoside Rg3 by detecting VEGFmRNA l VEGF protein 1eve1 and microvascu1ar density. Methods:Afterdeveloping human ovarian carcinoma SK0V3 ce11 mode1s in SCID mice,the mice were administered Rg3 (300ug/400u1/mouse) p. o., and micewith PBS p. o. or without Rg3 or PBS were used as controls. Tumora1vo1ume, metastasis, ascite, VEGF mRNA, VEGF protein andmicrovascu1ar density among 3 groups were detected and compared.The 1evels of VEGF mRNA of tumor tissue were determined byre1ative Quantative RT--PCR, and the VEGF protein 1eve1s of seraand ascitic f1uids were determined by ELISA. Microvascu1ar densitywas ca1cu1ated by immunohistochemistry (anti--CD34). LDS test weredone by SPSS10. 0 for windows 98. Results: l. No ascite formed butmetastasis decreased in SK0V3/Rg3 group. 2. Expression of VEGF mRNAin SK0V3/Rg3 group was 1ower significant1y than that of bothcontrol groups(P<0. 05). 3. Serum VEGF 1evels(pg/ml) in SK0V3/Rg3group(14. 574 l 0.