过剩1
PI3K/AKT/mTOR通路
安普克
葡萄糖转运蛋白
二甲双胍
癌症研究
癌细胞
化学
葡萄糖摄取
细胞生长
癌症
激酶
细胞凋亡
生物化学
胰岛素
生物
医学
内科学
蛋白激酶A
作者
Anindita De,Ashish Wadhwani,. Sauraj,Parikshit Roychowdhury,Ji Hee Kang,Young Tag Ko,Gowthamarajan Kuppusamy
出处
期刊:Polymers
[MDPI AG]
日期:2023-02-16
卷期号:15 (4): 976-976
被引量:6
标识
DOI:10.3390/polym15040976
摘要
The “Warburg effect” provides a novel method for treating cancer cell metabolism. Overexpression of glucose transporter 1 (GLUT1), activation of AMP-activated protein kinase (AMPK), and downregulation of mammalian target of rapamycin (mTOR) have been identified as biomarkers of abnormal cancer cell metabolism. Metformin (MET) is an effective therapy for breast cancer (BC), but its efficacy is largely reliant on the concentration of glucose at the tumor site. We propose a WZB117 (a GLUT1 inhibitor)-OCMC (O-carboxymethyl-chitosan)-MET combo strategy for simultaneous GLUT1 and mTOR targeting for alteration of BC metabolism. WZB117 conjugated polymeric nanoparticles were 225.67 ± 11.5 nm in size, with a PDI of 0.113 ± 0.16, and an encapsulation of 72.78 6.4%. OCMC pH-dependently and selectively releases MET at the tumor site. MET targets the mTOR pathway in cancer cells, and WZB117 targets BCL2 to alter GLUT1 at the cancer site. WZB117-OCMC-MET overcomes the limitations of MET monotherapy by targeting mTOR and BCL2 synergistically. WZB117-OCMC-MET activates AMPK and suppresses mTOR in a Western blot experiment, indicating growth-inhibitory and apoptotic characteristics. AO/EB and the cell cycle enhance cellular internalization as compared to MET alone. WZB117-OCMC-MET affects cancer cells’ metabolism and is a promising BC therapeutic strategy.
科研通智能强力驱动
Strongly Powered by AbleSci AI