we demonstrated that sLRPEE is secreted binds specifically to Wnta

We examined the effect of Topotecan and Cisplatin on the cell viability of Caov 3 and A2780 cells by MTS analysis. We analyzed the Akt kinase action, VEGF and HIF 1 expression after Cisplatin and Topotecan with a Dub inhibitor western blot analysis. Moreover, we also evaluated the results of Cisplatin and Topotecan about the dissemination of ovarian cancer in vivo. We thus demonstrated that Topotecan inhibits VEGF transcriptional activation and Akt kinase activity after treatment in platinum resistant ovarian cancers. We solved how Topotecan increased the scientific activity in the platinum resistant ovarian cancer. These provide a reason for using Topotecan in clinical regimens directed at molecular targeting agents in platinum resistant ovarian cancers. We've previously noted that Akt inactivation sensitizes human ovarian cancer cells to Cisplatin and Paclitaxel. Thus, inhibition of antiapoptotic signs, including these treated by the Akt pathway, has been proposed as a promising technique to enhance the Meristem efficacy of conventional chemotherapeutic agents. Because the PI3/Aktcascade is associated with resistance, inhibition with this cascade using gene transfection was effective in reversing Cisplatin resistance. Tumor cells exude vascular endothelial growth factor, which increases the proliferation of endothelial cells resulting in tumor angiogenesis and subsequent tumor progression. Environmental stresses, for example chemotherapy up-regulate HIF 1 and VEGF signaling in cancer cells, ergo leading to enhanced angiogenic and tumorigenic potential. Among the numerous Akt substrates, the mammalian target of rapamycin is primarily implicated in the regulation of HIF 1 protein in the translocation level. Thus, Foretinib the inhibition of the VEGF stream will be more powerful for blocking Cisplatin resistance. But, little molecular agents which prevent the Akt and/or VEGF cascade haven't yet been discovered. Topotec an camptothecin, a water soluble camptothecin analog, is a new topoisomerase I inhibitor which is active against numerous human tumor cell lines and xenograft tumors. Topotecan in addition has demonstrated clinical activity in ovarian carcinoma, small cell and non small cell bronchogenic carcinomas and myeloid leukemia. Lately, Phase II trial showed that Topotecan is beneficial in both platinum sensitive and painful and platinum resistant ovarian cancers. Pre-clinical models have demonstrated that Topotecan can enhance platinum mediated cytotoxicity through inhibition of DNA repair. Moreover, it was reported that Topotecan induces apoptosis in human lung cancer cells, simply, by downregulating the PI3K Akt signaling pathway. These considerations led us to look at whether Topotecan prevents the PI3K/Akt signaling pathway in ovarian cancers. Moreover, we considered herein whether Topotecan inhibits HIF 1 protein accumulation by downregulation of the PI3k/ Akt mTOR pathway in Cisplatin immune ovarian cancers.