THZ2 Ameliorates Mouse Colitis and Colitis-Associated Colorectal Cancer
Sheng-Te Wang,
Ying-Ying Wang,
Jia-Rong Huang,
Yu-Bin Shu,
Ke He,
Zhi Shi
Affiliations
Sheng-Te Wang
Cancer Minimally Invasive Therapies Centre, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou 510632, China
Ying-Ying Wang
Cancer Minimally Invasive Therapies Centre, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou 510632, China
Jia-Rong Huang
Center for Chemical Biology and Drug Discovery, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510650, China
Yu-Bin Shu
Department of Cell Biology & Institute of Biomedicine, Guangdong Provincial Biotechnology & Engineering Technology Research Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Genomic Medicine Engineering Research Center of Ministry of Education, MOE Key Laboratory of Tumor Molecular Biology, National Engineering Research Center of Genetic Medicine, State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Ke He
Cancer Minimally Invasive Therapies Centre, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou 510632, China
Zhi Shi
Cancer Minimally Invasive Therapies Centre, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou 510632, China
Colorectal cancer is a global malignancy with a high incidence and mortality rate. THZ2, a small inhibitor targeted CDK7, could inhibit multiple human tumor growths including small cell lung cancer, triple-negative breast cancer, ovarian cancer. However, the effect of THZ2 on inflammation, especially on colitis-associated colorectal cancer, is still unknown. In this study, we assessed the anti-inflammatory and anti-tumor effect of THZ2 in the mouse models of dextran sulfate sodium (DSS)-induced acute colitis and azoxymethane (AOM)/DSS-induced colitis-associated colorectal cancer. We found that THZ2 ameliorated inflammatory symptoms, including bleeding and diarrhea, in mouse models of DSS-induced acute colitis and AOM/DSS-induced colorectal cancer. The results of Western blot and immunohistochemistry showed that THZ2 rescued the up-regulated expression of COX2, IL-6, β-catenin, and snail in the mouse models. Moreover, THZ2 inhibits the development of colorectal cancer in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer. Generally, THZ2 not only can inhibit DSS-induced colitis, but also can hinder AOM/DSS-induced colorectal cancer.
