Antiproliferative effects of interferon-alphaCon1 on ovarian clear cell adenocarcinoma in vitro and in vivo.

ABSTRACT

PURPOSE: We examined the antiproliferative effect of IFN-alphaCon1 and its mechanism on ovarian clear cell adenocarcinoma in vitro and in vivo. EXPERIMENTAL DESIGN: (a) The effects of IFN-alphaCon1 on growth, morphology, cell cycle, and type I IFN-alpha 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-alphaCon1 were not obvious. CONCLUSIONS: IFN-alphaCon1 suppresses tumor proliferation by inducing apoptosis, blocking the cell cycle, and inhibiting tumor angiogenesis. Our findings show that the clinical efficacy of IFN-alphaCon1 can be predicted by examining IFNAR-2 expression on tumor cells, and the efficacy of IFN-alphaCon1 treatment can be evaluated by measuring serum bFGF and IL-8 levels.