the EGF tyrosine kinase recept signals through direct recruitment of PIk

We examined the effect of Cisplatin and Topotecan on the cell viability of Caov 3 and A2780 cells by MTS assay. We analyzed the Akt kinase Conjugating enzyme inhibitor action, VEGF and HIF 1 expression after Cisplatin and Topotecan with a western blot analysis. Moreover, we also considered the results of Cisplatin and Topotecan on the dissemination of ovarian cancer in vivo. We thus demonstrated that Topotecan inhibits Akt kinase activity and VEGF transcriptional activation after treatment in platinum resistant ovarian cancers. We solved how Topotecan enhanced the medical activity within the platinum resistant ovarian cancer. These supply a basis for applying Topotecan in clinical regimens aimed at molecular targeting brokers in platinum resistant ovarian cancers. We have previously noted that Akt inactivation sensitizes human ovarian cancer cells to Cisplatin and Paclitaxel. For that reason, inhibition of antiapoptotic signals, such as those medicated by the Akt pathway, has been proposed as a Ribonucleic acid (RNA) promising technique to enhance the efficacy of conventional chemotherapeutic agents. Since the PI3/Aktcascade is associated with Cisplatin resistance, inhibition of the cascade applying gene transfection was effective in avoiding Cisplatin resistance. Tumor cells exude vascular endothelial growth factor, which escalates the proliferation of endothelial cells leading to subsequent tumor progression and tumor angiogenesis. Environmental stresses, for example chemotherapy upregulate HIF 1 and VEGF signaling in cyst cells, hence leading to increased angiogenic and tumorigenic potential. Among the numerous Akt substrates, the target of rapamycin has been mainly implicated in the regulation of HIF 1 protein at the translocation level. For that reason, the inhibition of the VEGF stream could be more efficient for blocking VX-661 Cisplatin resistance. However, small molecular agents which block the Akt and/or VEGF cascade haven't yet been discovered. Topotec an camptothecin, a water soluble camptothecin analog, is a novel topoisomerase I inhibitor which can be active against numerous human tumor cell lines and xenograft tumors. Topotecan has also shown clinical activity in ovarian carcinoma, small cell and non small cell bronchogenic carcinomas and myeloid leukemia. Recently, Phase II trial showed that Topotecan works well in both platinum painful and sensitive and platinum immune ovarian cancers. Pre-clinical models have shown that Topotecan can improve platinum mediated cytotoxicity through inhibition of DNA repair. Moreover, it had been reported that Topotecan induces apoptosis in human lung cancer cells, partly, 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 thus whether Topotecan inhibits HIF 1 protein accumulation by downregulation of the PI3k/ Akt mTOR pathway in Cisplatin immune ovarian cancers.