Enkhbat Tumenjin, Nishi Masaaki, Yoshikawa Kozo, Jun Higashijima, Tokunaga Takuya, Takasu Chie, Kashihara Hideya, Ishikawa Daichi, Tominaga Masahide, Shimada Mitsuo
Department of Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Department of Therapeutic Radiology Institute of Biomedical Sciences, The University of Tokushima Graduate School, Tokushima, Japan.
Anticancer Res. 2018 Nov;38(11):6247-6252. doi: 10.21873/anticanres.12980.
BACKGROUND/AIM: Epigallocatechin-3-gallate (EGCG) is a major polyphenolic component of green tea. EGCG plays a potential role in radio-sensitizing cancer cells. The combined effect of EGCG and radiation was investigated in a colorectal cancer cell line, focusing on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) autophagy signalling.
HCT-116 cells were treated with 12.5 μM EGCG for different periods of time, 2 Gy radiation, or both. Cell viability was determined with the WST-8 assay. The number of colonies was determined with the colony formation assay. mRNA expression of LC3 and caspase-9 was analyzed with quantitative real-time polymerase chain reaction.
Combination treatment with EGCG and radiation significantly decreased the growth of HCT-116 cells. The number of colonies was reduced to 34.2% compared to the control group. Immunofluorescence microscopy images showed that nuclear translocation of Nrf2 was significantly increased when cells were treated with the combination of EGCG and radiation compared to the control and single-treatment groups. Combined treatment with EGCG and radiation significantly induced LC3 and caspase-9 mRNA expression.
EGCG increased the sensitivity of colorectal cancer cells to radiation by inhibiting cell proliferation and inducing Nrf2 nuclear translocation and autophagy.
背景/目的:表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶的主要多酚成分。EGCG在使癌细胞对放疗增敏方面发挥潜在作用。本研究在大肠癌细胞系中探究了EGCG与放疗的联合作用,重点关注核因子(红系衍生2)样2(Nrf2)自噬信号通路。
用12.5 μM EGCG处理HCT-116细胞不同时间,或进行2 Gy放疗,或二者联合处理。采用WST-8法测定细胞活力。采用集落形成试验测定集落数量。用定量实时聚合酶链反应分析LC3和半胱天冬酶-9的mRNA表达。
EGCG与放疗联合处理显著降低了HCT-116细胞的生长。与对照组相比,集落数量减少至34.2%。免疫荧光显微镜图像显示,与对照组和单处理组相比,EGCG与放疗联合处理的细胞中Nrf2的核转位显著增加。EGCG与放疗联合处理显著诱导了LC3和半胱天冬酶-9的mRNA表达。
EGCG通过抑制细胞增殖、诱导Nrf2核转位和自噬增加了大肠癌细胞对放疗的敏感性。