An up-to-date anti-cancer treatment strategy focusing on HIF-1alpha suppression: its application for refractory ovarian cancer.
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.
Fujita
Mariko
M
Department of Pathology, Tokai University School of Medicine, Japan.
Yasuda
Masanori
M
Kitatani
Kanae
K
Miyazawa
Masaki
M
Hirabayashi
Kenichi
K
Takekoshi
Susumu
S
Iida
Tetsuji
T
Hirasawa
Takeshi
T
Murakami
Masaru
M
Mikami
Mikio
M
Ishiwata
Isamu
I
Shimizu
Michio
M
Osamura
R Yoshiyuki
RY