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KMID : 0603520000050030144
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Journal of Korean Association of Cancer Prevention
2000 Volume.5 No. 3 p.144 ~ p.153
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Effects of Mitomycin-C, Cisplatin, and Vinblastine on Natural Killer Cell Activity in Mice
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Kang Heon-Joong
Kim Kwang-Hyuk
Rhew Hyun-Yul
Park Kun-Young
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Abstract
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Natural killer (NK) cells play a central role in immune surveillance against tumors and viral infection. In this study, we investigated the effect of various clinically used chemotherpeutic agents on NK cell activity. Splenic mononuclear cells from healthy normal mice, C57BL/6, were tested for their cytotoxic activity in vitro in the presence of mitomycin C, cisplatin, and vinblastine used for treatment of urologic tumors. Also, normal mice were intravenously injected with these agents for in vivo tests. Using MTT assay, natural killer (NK) cell-mediated growth inhibition of tumor cell was measured in normal and agents-exposed groups. Non-adherent splenocytes of normal or agents- exposed groups were cultured with Yac-1 cells at two different effector/target (E/T) cell ratios of 200/1 and 100/1 in an assay volume of 0.2 ml. After the optical density of culture wells containing MTT solution was measured at a wavelength of 540 nm, the percentage of dead cells relative to the control target cell number was calculated. Mitomycin-C and cisplatin suppressed the NK activity of mouse splenic mononuclear cells in vitro, whereas vinblastine enhanced or suppressed its activity according to doses with showing enhancement at 1.0 and 10.0μg and suppression at 0.1μg. In mice injected with these agents, mitomycin-C and cisplatin enhanced the NK activity by twice injections, vinblastine by once and three times injections. In contrast, its activity was suppressed by once injection with mitomycin-C or cisplatin, and by twice injectons with vinblastine. Therefore, the NK cell activity by exposure with anti-tumor agents shows differences according to kinds and doses of drug, and injection number in vivo. It was concluded that vinblastine had a higher effectiveness than mitomycin-C or cisplatin by showing augmentation of NK cell activity both in vitro and in vivo.
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KEYWORD
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Natural killer cell activity, Cisplatin, Mitomycin-C, Vinblastine, C57BL/6 mouse
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