An up-to-date anti-cancer treatment strategy focusing on HIF-1alpha suppression: its application for refractory ovarian cancer.

Abstract

Hypoxia inducible factor-1alpha (HIF-1alpha) 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-1alpha 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-1alpha 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-1alpha 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-1alpha was analyzed by immunohistochemistry and western blotting. It was demonstrated that inhibition of HIF-1alpha and vascular endothelial growth factor (VEGF) expressions would lead to the down-regulation of tumor cell proliferation. 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-1alpha and VEGF.

• Authors: Mariko Fujita, Masanori Yasuda, Kanae Kitatani, Masaki Miyazawa, Kenichi Hirabayashi, Susumu Takekoshi, Tetsuji Iida, Takeshi Hirasawa, Masaru Murakami, Mikio Mikami, Isamu Ishiwata, Michio Shimizu, R Yoshiyuki Osamura
• Journal: Acta histochemica et cytochemica (Acta Histochem Cytochem) Vol. 40 Issue 5 Pg. 139-42 (Dec 18 2007) ISSN: 0044-5991 [Print] Japan
• PMID: 18224245 (Publication Type: Journal Article)