GSK2606414 Sensitizes ABCG2-Overexpressing Multidrug-Resistant Colorectal Cancer Cells to Chemotherapeutic Drugs.
Ze-Zhong YuBu-Qing XuYing-Ying WangPeng-Wei ZhangYu-Bin ShuZhi ShiPublished in: Biomedicines (2023)
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 ABCG2 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.
Keyphrases
- multidrug resistant
- drug resistant
- molecular docking
- cancer stem cells
- acinetobacter baumannii
- gram negative
- signaling pathway
- pi k akt
- klebsiella pneumoniae
- drug delivery
- emergency department
- escherichia coli
- risk assessment
- risk factors
- gene expression
- coronary artery disease
- pseudomonas aeruginosa
- locally advanced
- cardiovascular events
- climate change
- molecular dynamics simulations
- dna methylation
- copy number
- human health
- endoplasmic reticulum stress
- dna binding
- cancer therapy