title: GRIM-19 inhibits the STAT3 signaling pathway and sensitizes gastric cancer cells to radiation.
abstract: Gastric cancer is one of the most common malignancies, and radiation resistance is one of the key obstacles in gastric cancer treatment. In this study, we demonstrate that "genes associated retinoid-IFN induced mortality-19" (GRIM-19) expression was lower in patients with radiotherapy-resistant tumors compared to patients with radiotherapy-sensitive tumors. In order to further investigate the effects of GRIM-19 expression on the radiation response in gastric cancer cells, we established BGC-803 clones stably expressing exogenous GRIM-19. We found that the percentage of apoptotic cells was higher in cells expressing GRIM-19 than untransfected cells post-radiation treatment. Furthermore, caspase-3, -8, and -9 activity was significantly increased in GRIM-19-expressing cells compared to untransfected cells after radiation. Finally, we demonstrate that expression of GRIM-19 in BGC-803 cells suppresses accumulation of STAT3. Collectively, these data show that GRIM-19 expression sensitizes BGC-803 cells to radiation, and this is likely due to suppression of STAT3 accumulation. In summary, our results indicate that GRIM-19 expression might be a useful therapy to enhance apoptosis in gastric cancer cells in response to radiation treatment.
authors.affiliation: Department of General Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110004, PR China. SJ_BuXM@163.com
authors.forename: Xianmin
authors.initials: X
authors.lastname: Bu
authors.forename: Chenghai
authors.initials: C
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D014965:X-Rays
chemical_list: D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human; D020169:Caspases