Downregulation of aryl hydrocarbon receptor expression decreases gastric cancer cell growth and invasion.
Downregulation of aryl hydrocarbon receptor expression decreases gastric cancer cell growth and invasion.
复制标题
芳基烃受体表达的下调可减少胃癌细胞的生长和侵袭。
DOI：
10.3892/or.2013.2410
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发表时间：
2013-07
期刊：
影响因子：
4.2
通讯作者：
Chen, Min-Hu
中科院分区：
文献类型：
--
作者：
Yin, Xiao-Fei;Chen, Jie;Mao, Wei;Wang, Yu-Hong;Chen, Min-Hu
芳烃受体（Aryl Hydrocarbon Receptor，AhR）是一种与肿瘤发生和发展相关的配体激活的转录因子。胃癌组织和胃癌细胞株中AhR表达明显增高，但AhR与胃癌的关系尚不清楚。本研究通过RNA干扰技术（RNAi）抑制AhR基因表达，探讨其对胃癌细胞（MKN 45和SGC 7901）生物学行为的影响，阐明AhR在胃癌发生发展中的具体作用机制。结果表明，针对AhR的小干扰RNA（siRNA）能有效抑制AhR的表达，并降低AhR通路的经典靶基因细胞色素P450（CYP）1A 1和CYP 1B 1的表达。与阴性对照组相比，转染AhR-siRNA的细胞生长速度减慢，G1-S期进程延迟，凋亡率增加。siRNA抑制SGC 7901细胞中AhR的表达可导致细胞迁移和侵袭能力下降，并伴有基质金属蛋白酶（MMP）-2和MMP-9的表达和活性下调。因此，我们的研究结果表明，AhR促进胃癌细胞的生长和侵袭力，AhR可能作为一个有前途的治疗胃癌的目标。
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor associated with tumor initiation and progression. AhR expression is significantly increased in gastric cancer tissues and gastric cancer cell lines; however, the relationship between AhR and gastric cancer is still unclear. In the present study, we explored the effects of the inhibition of AhR expression by RNA interference on the biological behavior of gastric cancer cells (MKN45 and SGC7901), and elucidated the specific mechanisms of AhR action in the development of gastric cancer. Results showed that small interfering RNA (siRNA) against AhR effectively inhibited the expression of AhR, and decreased the expression of cytochrome P450 (CYP)1A1 and CYP1B1, which are classic target genes of the AhR pathway. Compared to the negative control group, AhR-siRNA-transfected cells showed decreased cellular growth, delayed G1-S cell cycle progression and increased apoptosis rate. Furthermore, inhibition of AhR expression by siRNA in SGC7901 cells led to decreased cell migratory and invasive ability, accompanied by downregulation of expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9. Our results, therefore, suggest that AhR promotes the growth and invasiveness of gastric cancer cells and AhR may serve as a promising therapeutic target for gastric cancer.
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影响因子：
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