Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
J Exp Clin Cancer Res. 2012 May 16;31(1):46. doi: 10.1186/1756-9966-31-46.
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor associated with gastric carcinogenesis. 3,3'-Diindolylmethane (DIM) is a relatively non-toxic selective AhR modulator. This study was to detect the effects of DIM on gastric cancer cell growth.
Gastric cancer cell SGC7901 was treated with DIM at different concentrations (0,10,20,30,40,50 μmol/L) with or without an AhR antagonist, resveratrol. The expression of AhR and Cytochrome P4501A1 (CYP1A1), a classic target gene of AhR pathway, were detected by RT-PCR and Western blot; cell viability was measured by MTT assay, and the changes in cell cycle and apoptosis were analyzed by flow cytometry.
RT-PCR and western-blot showed that with the increase of the concentration of DIM, AhR protein gradually decreased and CYP1A1 expression increased, suggesting that DIM activated the AhR pathway and caused the translocation of AhR from cytoplasm to nucleus. MTT assay indicated that the viability of SGC7901 cells was significantly decreased in a concentration- and time-dependent manner after DIM treatment and this could be partially reversed by resveratrol. Flow cytometry analysis showed that DIM arrested cell cycle in G1 phase and induced cell apoptosis.
Selective aryl hydrocarbon receptor modulator 3,3'-Diindolylmethane inhibits SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle progression. AhR may be a potential therapeutic target for gastric cancer treatment.
芳香烃受体 (AhR) 是一种与胃癌发生相关的配体激活转录因子。3,3'-二吲哚甲烷 (DIM) 是一种相对无毒的选择性 AhR 调节剂。本研究旨在检测 DIM 对胃癌细胞生长的影响。
用不同浓度（0、10、20、30、40、50μmol/L）的 DIM 处理胃癌细胞 SGC7901，同时用 AhR 拮抗剂白藜芦醇处理。通过 RT-PCR 和 Western blot 检测 AhR 和细胞色素 P4501A1（CYP1A1）的表达，CYP1A1 是 AhR 通路的经典靶基因；通过 MTT 法测定细胞活力，通过流式细胞术分析细胞周期和凋亡的变化。
RT-PCR 和 Western blot 结果显示，随着 DIM 浓度的增加，AhR 蛋白逐渐减少，CYP1A1 表达增加，提示 DIM 激活了 AhR 通路，导致 AhR 从细胞质向核内易位。MTT 法表明，DIM 处理后 SGC7901 细胞的活力呈浓度和时间依赖性显著降低，白藜芦醇可部分逆转这种作用。流式细胞术分析显示，DIM 将细胞周期阻滞在 G1 期并诱导细胞凋亡。
选择性芳香烃受体调节剂 3,3'-二吲哚甲烷通过诱导细胞凋亡和延缓细胞周期进程抑制 SGC7901 细胞增殖。AhR 可能是胃癌治疗的潜在治疗靶点。
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