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Antiproliferative Effects of Interferon-Con1 on Ovarian Clear Cell Adenocarcinoma In vitro and In vivo

Departments of ¹ Pathology and ² Obstetrics and Gynecology, Kurume University School of Medicine, Research Center of Innovative Cancer Therapy of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Fukuoka, Japan

Purpose: We examined the antiproliferative effect of IFN-Con1 and its mechanism on ovarian clear cell adenocarcinoma in vitro and in vivo.

Experimental Design: (a) The effects of IFN-Con1 on growth, morphology, cell cycle, and type I IFN- receptor (IFNAR-2) expression were examined on two ovarian clear cell adenocarcinoma cell lines (KOC-5C and KOC-7C) in vitro. (b) KOC-5C or KOC-7C cells were transplanted into nude mice, and changes in tumor volume, tumor weight, apoptosis, necrosis, and microvessel density were investigated. The expression of angiogenesis factors was examined in the serum and the developed tumors.

Results: Both cell lines expressed IFNAR-2 mRNA, but its protein was detected only in KOC-7C. In KOC-7C cells, antiproliferative effects were observed in a time- and dose-dependent manner and cell division was blocked at the S phase. The KOC-7C tumors showed decreases in tumor volume and weight; a decreasing tendency in basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and interleukin (IL)-8 protein expression in the tumor; a significant decrease in bFGF and IL-8 protein expression in the serum, and of microvessel density; and significant increase in apoptosis and necrosis in the tumor. In the KOC-5C tumors, these in vitro and in vivo changes were not apparent, and the antiproliferative effects of IFN-Con1 were not obvious.

Conclusions: IFN-Con1 suppresses tumor proliferation by inducing apoptosis, blocking the cell cycle, and inhibiting tumor angiogenesis. Our findings show that the clinical efficacy of IFN-Con1 can be predicted by examining IFNAR-2 expression on tumor cells, and the efficacy of IFN-Con1 treatment can be evaluated by measuring serum bFGF and IL-8 levels.