title: Downregulation of aryl hydrocarbon receptor expression decreases gastric cancer cell growth and invasion.
abstract: 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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Yin
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Mao
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Min-Hu
authors.initials: MH
authors.lastname: Chen
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D065633:Cytochrome P-450 CYP1B1; D015536:Down-Regulation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D001189:Aryl Hydrocarbon Hydroxylases; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9