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KMID : 0615720170340010001
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Jouranl of Korean Acupuncture and Moxibustion society
2017 Volume.34 No. 1 p.1 ~ p.9
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Synergistic Effects of Bee Venom and Natural Killer Cells on B16F10 Melanoma Cell Growth Inhibition through IL-4-mediated Apoptosis
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Sin Dae-Chul
Kang Mi-Suk
Song Ho-Sueb
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Abstract
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Objectives: We investigated the synergistic effects of bee venom (BV) and natural killer (NK) cells on B16F10 melanoma cell apoptosis mediated by IL-4.
Methods: We performed a cell viability assay to determine whether BV can enhance the inhibitory effect of NK-92MI cells on the growth of B16F10 melanoma cells, and western blot analysis to detect changes in the expression of IL-4, IL-4Rα, and other apoptosis-related proteins. EMSA was performed to observe the activity of STAT6. To confirm that the inhibitory effect of BV and NK cells was mediated by IL-4, the above tests were repeated after IL-4 silencing by siRNA (50 nM).
Results: B16F10 melanoma cells co-cultured with NK-92MI cells and simultaneously treated by BV (5 μg/ml) showed a higher degree of proliferation inhibition than when treated by BV (5 μg/ml) alone or co-cultured with NK-92MI cells alone. Expression of IL-4, IL-4Rα, and that of other pro-apoptotic proteins was also enhanced after co-culture with NK-92MI cells and simultaneous treatment with BV (5 μg/ml). Furthermore, the expression of anti-apoptotic bcl-2 decreased, and the activity of STAT6, as well as the expression of STAT6 and p-STAT6 were enhanced. IL-4 silencing siRNA (50 nM) in B16F10 cells, the effects of BV treatment and NK-92MI co-culture were reversed.
Conclusion: These results suggest that BV could be an effective alternative therapy for malignant melanoma by enhancing the cytotoxic and apoptotic effect of NK cells through an IL-4-mediated pathway.
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KEYWORD
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Bee Venom, Malignant Melanoma, IL-4, Natural Killer cell, Apoptosis
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