An Up-to-Date Anti-Cancer Treatment Strategy Focusing on HIF-1α Suppression : Its Application for Refractory Ovarian Cancer

概要

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Hypoxia inducible factor-1α (HIF-1α) predominantly determines the transcriptional activity of HIF-1, which induces the certain genetic expressions to participate in the proliferation and progression of the tumor. It is supposed that HIF-1α is also an extremely important factor in cancer treatment. Based on the results of our recent analyses using ovarian tumors, which indicated the close association of HIF-1α expression with the acquisition of malignancy and the characterization of histology, we further investigated the possibility of a new strategy of cancer therapy that targeted HIF-1α inhibition in the ovarian carcinoma. The cell line HUOCA-II, which originates from the refractory ovarian clear cell adenocarcinoma, was treated with rapamycin. The inhibitory effect of HIF-1α was analyzed by immunohistochemistry and western blotting. It was demonstrated that inhibition of HIF-1α and vascular endothelial growth factor (VEGF) expressions would lead to the down-regulation of tumor cellproliferation. Interestingly, there was little or no change in GLUT-1 expression by rapamycin administration. Thus, the inhibition of GLUT-1 may also be a key for the new strategy of cancer therapy as well as HIF-1α and VEGF.
日本組織細胞化学会の論文