A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells  

作　　者：SHAHID KARIM ALANOUD NAHER ALGHANMI MAHA JAMAL HUDA ALKREATHY ALAM JAMAL HIND A.ALKHATABI MOHAMMED BAZUHAIR AFTAB AHMAD 

机构地区：[1]Department of Clinical Pharmacology,Faculty of Medicine,King Abdulaziz University,Jeddah,Saudi Arabia [2]Department of Biochemistry,Faculty of Science,King Abdulaziz University,Jeddah,Saudi Arabia [3]Department of Biochemistry,College of Science,University of Jeddah,Jeddah,21959,Saudi Arabia [4]Health Information Technology Department,The Applied College,King Abdulaziz University,Jeddah,Saudi Arabia [5]Pharmacovigilance and Medication Safety Unit,Center of Research Excellence for Drug Research and Pharmaceutical Industries,King Abdulaziz University,Jeddah,Saudi Arabia

出　　处：《Oncology Research》2024年第5期817-830,共14页肿瘤学研究（英文）

基　　金：funded by the Deanship of Scientific Research(DSR),King Abdulaziz University,Jeddah,Saudi Arabia,under Grant No.KEP-1-166-41;The authors,therefore,acknowledge DSR,with thanks for their technical and financial support.

摘　　要：Cancer frequently develops resistance to the majority of chemotherapy treatments.This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro experimentation.The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 cells.Interestingly,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth.Notably,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate levels.Moreover,this effect was found to be dependent on the dosages of the drugs.In addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression.This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of DOX.The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

关 键 词：SGLT2 Cancer CYTOTOXICITY ATP Cell cycle 

分 类 号：R737.9[医药卫生—肿瘤]