Effects of naloxone on human ovarian cancer cell growth in vitro and in vivo.

Abstract

The effects of naloxone on human ovarian cancer cell growth in vitro and in vivo were examined by using an established cell line, designated KF, derived from human ovarian carcinoma. When the KF cells were incubated in the presence of various concentrations of naloxone for 72 hr, the cell proliferation was inhibited in a dose-dependent manner in the concentration range of 30 to 120 microM naloxone. The growth-inhibitory effect of naloxone could not be detected by 51Cr-release assay or colony-forming assay. The inhibition of cell proliferation by naloxone resulted from the inhibitory effect on protein synthesis in the KF cells, as confirmed by a marked decrease of incorporation of [3H]valine. In order to determine the effect of naloxone on tumor growth in vivo, ip injections 3 times a week of 2.5 or 5.0 mg/kg naloxone were initiated either one week prior to tumor inoculation (pretreated groups) or one week after tumor inoculation (post-treated groups). Nude mice in the pretreated groups had significantly smaller tumor volumes than those in the untreated group as long as naloxone was administered. On the other hand, in the post-treated groups a significant growth retardation was observed 2 weeks after initiation of treatment with 2.5 mg/kg naloxone. In comparison to a median survival time of 38 days for untreated controls, the naloxone pre- and post-treated groups showed increases of 26-71% in median survival.