PMID- 36933092 OWN - NLM STAT- MEDLINE DCOM- 20230328 LR - 20230329 IS - 1432-1211 (Electronic) IS - 0093-7711 (Linking) VI - 75 IP - 2 DP - 2023 Apr TI - Tumor necrosis factor-alpha induces proliferation and reduces apoptosis of colorectal cancer cells through STAT3 activation. PG - 161-169 LID - 10.1007/s00251-023-01302-y [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory factor that plays an important role in establishing a complicated connection between inflammation and cancer. TNF-alpha promotes tumor proliferation, migration, invasion, and angiogenesis according to numerous studies. Studies have shown the significant role of STAT3, a downstream transcription factor of another important inflammatory cytokine, IL-6 in the development and progression of different tumors especially colorectal cancer. In the present study, we investigated whether TNF-alpha has a role in proliferation and apoptosis of colorectal cancer cells through STAT3 activation. HCT116 cell line as human colorectal cancer cells was used in this study. Major assays were MTT assay, reverse transcription-PCR (RT-PCR), flow cytometric analysis, and ELISA. Results showed that TNF-alpha significantly increased the phosphorylation of STAT3 and expression of all the STAT3 target genes related to cell proliferation, survival, and metastasis compared with control. Moreover, our data showed that the STAT3 phosphorylation and expression of its target genes significantly were reduced in the presence of TNF-alpha + STA-21 compared with TNF-alpha-treated group demonstrating that the increase in genes expression partially was due to the TNF-alpha-induced STAT3 activation. On the other hand, STAT3 phosphorylation and mRNA levels of its target genes were partially decreased in the presence of TNF-alpha + IL-6R supporting the indirect pathway of STAT3 activation by TNF-alpha through inducing IL-6 production in cancer cells. Given the growing evidence for STAT3 as a key mediator of inflammation-induced colon cancer, our findings support further investigation of STAT3 inhibitors as potential cancer therapies. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Wei, Wei AU - Wei W AD - Department of Pathology, Xi'an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, 710018, People's Republic of China. FAU - Wang, Juanhong AU - Wang J AD - Department of Pathology, Xi'an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, 710018, People's Republic of China. FAU - Huang, Pu AU - Huang P AD - Department of Pathology, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi, 710021, People's Republic of China. FAU - Gou, Siqi AU - Gou S AD - Department of Pathology, Xi'an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, 710018, People's Republic of China. FAU - Yu, Daihua AU - Yu D AD - Department of Critical Care Medicine, Xi'an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, 710018, People's Republic of China. FAU - Zong, Lei AU - Zong L AUID- ORCID: 0000-0002-3044-4476 AD - Department of Critical Care Medicine, Xi'an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, 710018, People's Republic of China. zonglei7910@sina.com. LA - eng PT - Journal Article DEP - 20230318 PL - United States TA - Immunogenetics JT - Immunogenetics JID - 0420404 RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Interleukin-6) RN - 0 (STAT3 protein, human) RN - 0 (STAT3 Transcription Factor) SB - IM MH - Humans MH - *Tumor Necrosis Factor-alpha/genetics MH - Interleukin-6/genetics MH - Cell Proliferation MH - Apoptosis MH - *Colorectal Neoplasms/genetics/metabolism/pathology MH - Inflammation MH - STAT3 Transcription Factor/genetics/metabolism OTO - NOTNLM OT - Colorectal cancer OT - IL-6 OT - STAT3 OT - TNF- alpha EDAT- 2023/03/19 06:00 MHDA- 2023/03/28 17:16 CRDT- 2023/03/18 12:15 PHST- 2023/01/14 00:00 [received] PHST- 2023/02/14 00:00 [accepted] PHST- 2023/03/28 17:16 [medline] PHST- 2023/03/19 06:00 [pubmed] PHST- 2023/03/18 12:15 [entrez] AID - 10.1007/s00251-023-01302-y [pii] AID - 10.1007/s00251-023-01302-y [doi] PST - ppublish SO - Immunogenetics. 2023 Apr;75(2):161-169. doi: 10.1007/s00251-023-01302-y. Epub 2023 Mar 18.