inability to replicate spread to neighboring tum cells

A2780 cells by MTS analysis and we examined the effect of Cisplatin and Topotecan on the cell viability of Caov 3. We examined the Akt kinase exercise, VEGF and HIF 1 expression after Cisplatin Lenalidomide and Topotecan with a western blot analysis. More over, we also considered the consequences of Topotecan and Cisplatin to the intra-abdominal dissemination of ovarian cancer in vivo. We herein demonstrated that Topotecan inhibits Akt kinase activity and VEGF transcriptional activation after therapy in platinum resistant ovarian cancers. We clarified how Topotecan enhanced the medical activity within the jewelry resistant ovarian cancer. These give a basis for applying Topotecan in clinical regimens directed at molecular targeting brokers in platinum resistant ovarian cancers. We've previously noted that Akt inactivation sensitizes human ovarian cancer cells to Cisplatin and Paclitaxel. Therefore, inhibition of antiapoptotic signs, such as these treated by the Akt pathway, is Gene expression proposed as a promising strategy to improve the efficacy of conventional chemotherapeutic agents. Because the PI3/Aktcascade is involved with resistance, inhibition of this cascade applying gene transfection was effective in treating Cisplatin resistance. Tumor cells secrete vascular endothelial growth factor, which increases the proliferation of endothelial cells resulting in subsequent tumor development and tumor angiogenesis. Environmental stresses, such as for example chemotherapy up-regulate HIF 1 and VEGF signaling in tumor cells, hence leading to improved tumorigenic and angiogenic potential. Among the numerous Akt substrates, Cediranib the mammalian target of rapamycin is mainly implicated in the regulation of HIF 1 protein in the translocation level. Thus, the inhibition of the VEGF cascade may well be more helpful for blocking Cisplatin resistance. However, little molecular agents which block the Akt and/or VEGF cascade have not yet been found. Topotec an camptothecin, a water-soluble camptothecin analog, is a new topoisomerase I inhibitor which can be active against numerous human tumor cell lines and xenograft tumors. Topotecan in addition has shown clinical activity in ovarian carcinoma, small cell and non small cell bronchogenic carcinomas and myeloid leukemia. Recently, Phase II trial showed that Topotecan is beneficial in both platinum painful and sensitive and platinum resistant ovarian cancers. Preclinical models have shown that Topotecan can increase platinum mediated cytotoxicity through inhibition of DNA repair. Moreover, it had been claimed that Topotecan induces apoptosis in human lung cancer cells, in part, by downregulating the PI3K Akt signaling pathway. These considerations light emitting diode us to examine whether Topotecan inhibits the PI3K/Akt signaling pathway in ovarian cancers. Furthermore, we evaluated thus whether Topotecan inhibits HIF 1 protein accumulation by downregulation of the PI3k/ Akt mTOR pathway in Cisplatin resistant ovarian cancers.