An Up-to-date Anti-cancer Treatment Strategy Focusing on HIF-1alpha Suppression: Its Application for Refractory Ovarian Cancer

Overview

Journal Acta Histochem Cytochem

Specialty Biochemistry

Date 2008 Jan 29

PMID 18224245

Citations 6

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

Affiliations

Soon will be listed here.

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.

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