Dorsomorphin attenuates ABCG2-mediated multidrug resistance in colorectal cancer.

Autor:	Li XP; Cancer Minimally Invasive Therapies Centre, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, China.; Department of Cell Biology and Institute of Biomedicine, Guangdong Provincial Biotechnology and 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, China., Cao LQ; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Institute of Neuroscience, Guangzhou Medical University, Guangzhou, China., Yu ZZ; Cancer Minimally Invasive Therapies Centre, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, China.; Department of Cell Biology and Institute of Biomedicine, Guangdong Provincial Biotechnology and 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, China., He K; Cancer Minimally Invasive Therapies Centre, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, China., Ding PB; Department of Cell Biology and Institute of Biomedicine, Guangdong Provincial Biotechnology and 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, China., Li JS; Department of Cell Biology and Institute of Biomedicine, Guangdong Provincial Biotechnology and 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, China., Shan YY; Department of Cell Biology and Institute of Biomedicine, Guangdong Provincial Biotechnology and 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, China., Su YB; Department of Cell Biology and Institute of Biomedicine, Guangdong Provincial Biotechnology and 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, China., Yuan ZM; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Shi Z; Cancer Minimally Invasive Therapies Centre, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, China.; Department of Cell Biology and Institute of Biomedicine, Guangdong Provincial Biotechnology and 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, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 May 24; Vol. 15, pp. 1393693. Date of Electronic Publication: 2024 May 24 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1393693
Abstrakt:	Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Li, Cao, Yu, He, Ding, Li, Shan, Su, Yuan and Shi.)
Databáze:	MEDLINE
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