GSK2606414使过表达ABCG2的多药耐药结肠癌细胞对化疗药物敏感。
GSK2606414 Sensitizes ABCG2-Overexpressing Multidrug-Resistant Colorectal Cancer Cells to Chemotherapeutic Drugs.
作者信息
Yu Ze-Zhong, Xu Bu-Qing, Wang Ying-Ying, Zhang Peng-Wei, Shu Yu-Bin, Shi Zhi
机构信息
Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
出版信息
Biomedicines. 2023 Nov 20;11(11):3103. doi: 10.3390/biomedicines11113103.
Colorectal cancer is a common malignant tumor. A major factor in the high mortality rate of colorectal cancer is the emergence of multidrug resistance (MDR). Overexpression of the gene in cancer cells directly leads to MDR. Finding new inhibitors of ABCG2 may be an effective way to overcome drug resistance. We found that the compound GSK2606414 enhanced the sensitivity of the ABCG2 substrate to the chemotherapeutic drugs mitoxantrone and doxorubicin in ABCG2-overexpressing multidrug-resistant colorectal cancer cells by increasing their intracellular accumulation without affecting the protein expression of ABCG2. Molecular docking experiments predicted that GSK2606414 could stably bind in the drug-binding pocket of ABCG2. In conclusion, GSK2606414 can sensitize ABCG2-overexpressed multidrug-resistant colorectal cancer cells to chemotherapy drugs and can be used as a potential inhibitor of ABCG2.
结直肠癌是一种常见的恶性肿瘤。结直肠癌高死亡率的一个主要因素是多药耐药性（MDR）的出现。癌细胞中该基因的过表达直接导致多药耐药性。寻找新的ABCG2抑制剂可能是克服耐药性的有效方法。我们发现，化合物GSK2606414通过增加ABCG2过表达的多药耐药结直肠癌细胞内化疗药物米托蒽醌和阿霉素的积累，增强了ABCG2底物对这些化疗药物的敏感性，且不影响ABCG2的蛋白表达。分子对接实验预测GSK2606414可稳定结合在ABCG2的药物结合口袋中。总之，GSK2606414可使ABCG2过表达的多药耐药结直肠癌细胞对化疗药物敏感，可作为ABCG2的潜在抑制剂。
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