白藜芦醇与 TK/GCV 疗法对黑素瘤细胞的协同抑制作用。
Synergistic inhibitory effect of resveratrol and TK/GCV therapy on melanoma cells.
机构信息
Department of Medical Biotechnology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Research Center for Integrative Medicine of Guangzhou University of Chinese Medicine, Key Laboratory of Chinese MedicinePathogenesis and Therapy Research), School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
出版信息
J Cancer Res Clin Oncol. 2020 Jun;146(6):1489-1499. doi: 10.1007/s00432-020-03203-z. Epub 2020 Apr 3.
PURPOSE
To investigate the synergistic effect of resveratrol on the bystander effect of TK/GCV suicide gene system in melanoma cells.
METHODS
The effect of resveratrol on the growth of B16 cells and the synergistic effect of resveratrol with or without GCV were detected by MTT assay and high content screening assay. The effect of resveratrol on GJIC function was detected by flow cytometry combined with fluorescence tracer and fluorescence microscope, and the expression of gap junction protein was detected by western blotting. Synergistic killing effect of resveratrol plus TK/GCV was tested in vivo using transplanted melanoma model.
RESULTS
In vitro, resveratrol can enhanced GJ function and upregulated Cx32 and Cx43 protein expression in B16 cells. Resveratrol synergized with GCV to kill mixed B16 melanoma cells (20% TK cells and 80% TK cells) and to improve apoptosis rate of TK cells (the bystander effect of TK system), and the synergistic action was reversed by the GJ inhibitor AGA. In vivo, when B16 cells were mixed with 30% TK B16 cells, significantly reduced tumor weight and volume were observed after combinational treatment with resveratrol plus GCV as compared with GCV or resveratrol treatment alone.
CONCLUSIONS
Resveratrol could synergistically enhance the killing effect of TK/GCV suicide gene system in melanoma B16 cells and transplanted melanoma. It might be a promising adjuvant of TK/GCV therapy.
目的
研究白藜芦醇对黑素瘤细胞 TK/GCV 自杀基因系统旁观者效应的协同作用。
方法
MTT 法和高通量筛选法检测白藜芦醇对 B16 细胞生长的影响，以及白藜芦醇与 GCV 联合应用的协同作用。流式细胞术结合荧光示踪和荧光显微镜检测白藜芦醇对 GJIC 功能的影响，western blot 检测缝隙连接蛋白的表达。体内移植性黑素瘤模型检测白藜芦醇联合 TK/GCV 的协同杀伤作用。
结果
体外实验中，白藜芦醇能增强 B16 细胞的 GJ 功能，并上调 Cx32 和 Cx43 蛋白表达。白藜芦醇与 GCV 联合应用可协同杀伤混合 B16 黑素瘤细胞（20% TK 细胞和 80% TK 细胞），并提高 TK 细胞的凋亡率（TK 系统的旁观者效应），GJ 抑制剂 AGA 可逆转协同作用。体内实验中，当 B16 细胞与 30% TK B16 细胞混合时，与 GCV 或白藜芦醇单独治疗相比，白藜芦醇联合 GCV 治疗可显著降低肿瘤重量和体积。
结论
白藜芦醇可协同增强 TK/GCV 自杀基因系统对黑素瘤 B16 细胞及移植性黑素瘤的杀伤作用，可能成为 TK/GCV 治疗的一种有前途的辅助药物。
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