Yujiang Fang1,2,3, Xuhui Chen1,4, Qian Bai2, Chenglu Qin2,5, Abdimalik O Mohamud2, Ziwen Zhu2, Tyler W Ball2, Caleb M Ruth2, Dylan R Newcomer2, Elizabeth J Herrick2, Michael B Nicholl2,3. 1. Department of Microbiology & Immunology, Des Moines University, Des Moines, Iowa. 2. Department of Surgery, University of Missouri School of Medicine, Columbia, Missouri. 3. Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, Missouri. 4. Department of Surgery, Luohu Hospital, Shenzhen, China. 5. Department of Gynecology & Obstetrics, Luohu Hospital, Shenzhen, China.
Abstract
BACKGROUND: IL-9 is a pleiotropic cytokine produced mainly by Th9 cells. IL-9 may have an anti-proliferative role in murine melanoma, however, its effect on human melanoma is unknown. METHODS: We examined the effects of IL-9 on proliferation and apoptosis in four human melanoma cell lines, HTB-65, HTB-72, CRL-11147, and SK-Mel-5. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis, as appropriate. RESULTS: We found that IL-9 decreased the percentage of colonies of HTB-72 and SK-Mel-5 cells but not that of HTB-65 or CRL-11147 cells. PCNA mRNA, PCNA+ cells, PCNA staining intensity, and the OD value of HTB-72 melanoma cells were consistently decreased in the present of IL-9. IL-9 also increased TUNEL+ cells and the relative caspase-3 activity in HTB-72 melanoma cells. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. The anti-proliferative effect of IL-9 on HTB-72 cells correlated with higher expression of anti-proliferative molecule p21. Its pro-apoptotic effect on HTB-72 cells correlated with higher expression of the pro-apoptotic molecule TRAIL. CONCLUSIONS: IL-9 inhibits melanoma HTB-72 cell growth by upregulation of p21 and TRAIL. Understanding the interactions between IL-9 and melanoma may help direct strategies for cytokine-based immunotherapy development.
BACKGROUND:IL-9 is a pleiotropic cytokine produced mainly by Th9 cells. IL-9 may have an anti-proliferative role in murinemelanoma, however, its effect on humanmelanoma is unknown. METHODS: We examined the effects of IL-9 on proliferation and apoptosis in four humanmelanoma cell lines, HTB-65, HTB-72, CRL-11147, and SK-Mel-5. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis, as appropriate. RESULTS: We found that IL-9 decreased the percentage of colonies of HTB-72 and SK-Mel-5 cells but not that of HTB-65 or CRL-11147 cells. PCNA mRNA, PCNA+ cells, PCNA staining intensity, and the OD value of HTB-72 melanoma cells were consistently decreased in the present of IL-9. IL-9 also increased TUNEL+ cells and the relative caspase-3 activity in HTB-72 melanoma cells. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. The anti-proliferative effect of IL-9 on HTB-72 cells correlated with higher expression of anti-proliferative molecule p21. Its pro-apoptotic effect on HTB-72 cells correlated with higher expression of the pro-apoptotic molecule TRAIL. CONCLUSIONS:IL-9 inhibits melanoma HTB-72 cell growth by upregulation of p21 and TRAIL. Understanding the interactions between IL-9 and melanoma may help direct strategies for cytokine-based immunotherapy development.
Authors: Alicia A Manning; Lei Zhao; Ziwen Zhu; Huaping Xiao; Chase G Redington; Vivi A Ding; Theodore Stewart-Hester; Qian Bai; Jacob Dunlap; Mark R Wakefield; Yujiang Fang Journal: Med Oncol Date: 2018-12-01 Impact factor: 3.064
Authors: Yujiang Fang; Lei Zhao; Huaping Xiao; Kathryn M Cook; Qian Bai; Elizabeth J Herrick; Xuhui Chen; Chenglu Qin; Ziwen Zhu; Mark R Wakefield; Michael B Nicholl Journal: Med Oncol Date: 2017-01-05 Impact factor: 3.064
Authors: Vivi A Ding; Ziwen Zhu; Timothy A Steele; Mark R Wakefield; Huaping Xiao; Dean Balabanov; Yujiang Fang Journal: Med Oncol Date: 2017-12-05 Impact factor: 3.064
Authors: Ziwen Zhu; Kristoffer T Davidson; Andrew Brittingham; Mark R Wakefield; Qian Bai; Huaping Xiao; Yujiang Fang Journal: Med Oncol Date: 2016-09-08 Impact factor: 3.064