文献类型：期刊文献

英文题名：Targeting CD133 reverses drug-resistance via the AKT/NF-κB/MDR1 pathway in colorectal cancer

作者：Yuan, Zeting[1,2];Liang, Xin[3,4];Zhan, Yueping[5];Wang, Ziyuan[6];Xu, Jian[5];Qiu, Yanyan[1];Wang, Jie[7];Cao, Yijun[7];Le, Van-Minh[8];Ly, Hai-Trieu[8];Xu, Jianhua[1];Li, Wei[7];Yin, Peihao[1,2,7];Xu, Ke[1,2,5]

机构：[1]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China;[2]Anhui Med Univ, Shanghai Putuo Cent Sch Clin Med, Hefei 230032, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China;[5]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Cent Lab, Shanghai 200062, Peoples R China;[6]Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Pathol, Shanghai, Peoples R China;[7]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Gen Surg, Shanghai 200062, Peoples R China;[8]Natl Inst Med Mat, Res Ctr Ginseng & Med Mat CGMM, Ho Chi Minh City 70000, Vietnam

年份：2020

卷号：122

期号：9

起止页码：1342

外文期刊名：BRITISH JOURNAL OF CANCER

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000520035700001)】；

基金：This project was sponsored by the National Nature Science Foundation of China (81873137, 81973700, 81703885), by Shanghai Rising-Star Program (17QA1403400). This project was also sponsored by "the twelfth five year" key subject (Integrated Chinese and Western Medicine and General practice training of Traditional Chinese Medicine) of traditional Chinese medicine of State Administration of Traditional Chinese medicine and the Action Plan of Shanghai Municipality for Further Accelerating the Development of Traditional Chinese Medicine [ZY (2018-2020)-RCPY-2016].

语种：英文

摘要：Background Recent studies have shown that multidrug resistance may be induced by the high stemness of cancer cells. Following prolonged chemotherapy, MDR protein 1 (MDR1) and CD133 increase in CRC, but the relationship between them is unclear. Methods The relationship between MDR and CSC properties in CRC was determined via CCK-8 assay, apoptosis assay, DOX uptake and retention, immunohistochemistry, immunofluorescence and flow cytometry. The correlations between their expression levels were evaluated using Spearman's rank statistical test and the Mann-Whitney test. Furthermore, the effect of CD133 on the repression of the AKT/NF-kappa B/MDR1 signalling pathway was investigated in vitro and in vivo. Results We found that CD133 increased with the emergence of drug-resistance phenotypes, and the high expression of MDR1/P-gp was consistently accompanied by positive expression of CD133 as demonstrated by the analysis of patient samples. Up- or downregulation of CD133 could regulate MDR via AKT/NF-kappa B/MDR1 signalling in CRC. A rescue experiment showed that the AKT/NF-kappa B signalling pathway is the main mechanism by which CD133 regulates MDR1/P-gp expression in CRC. Conclusions Taken together, our results suggest that targeting CD133 reverses drug resistance via the AKT/NF-kappa B/MDR1 pathway and that this pathway might serve as a potential therapeutic target to reverse MDR in CRC.