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Effect of Starvation in Reversing Cancer Chemoresistance Based on Drug-Resistance Detection by Dextran Nanoparticles
International Journal of Nanomedicine ( IF 8 ) Pub Date : 2020-11-20 , DOI: 10.2147/ijn.s283430
Chenglong Wang 1 , Xuzhu Gao 1 , Fanchen Wang 1 , Wencai Guan 1 , Hongjing Dou 2 , Guoxiong Xu 1
Affiliation  

Introduction: Chemoresistance leads to chemotherapy failure in patients with cancer. Multidrug resistance (MDR) in cancer is mainly caused by the high expression of P-glycoprotein encoded by the MDR1 gene, which is an ATP-dependent protease. Keeping the stronger invasion and migration abilities of chemoresistant cells in cancer also requires more ATP consumption. Herein, we aimed to reverse resistance by reducing the glucose supply in the cellular environment.
Methods: A starvation approach in reversing chemoresistance was applied, which was implemented through preparing fluorescent dextran-based nanoparticles to detect the proportion of chemoresistant cells in the chemoresistant/chemosensitive cell mixture after cells cultured in a low-glucose condition.
Results: Chemoresistant cells had higher glucose consumption with higher ATPase expression and stronger glucose dependence compared to chemosensitive cells. Moreover, cancer cells cultured in a low-glucose condition reduced the proportion of chemoresistant cells.
Conclusion: Starvation therapy can be used as a new method to reverse drug resistance in cancer.

Keywords: cancer drug-resistance, P-glycoprotein, starvation therapy, nanoparticles, resistance reversal


中文翻译:

基于葡聚糖纳米颗粒的耐药性检测,饥饿在逆转癌症化疗耐药中的作用

引言:化疗耐药导致癌症患者化疗失败。癌症中的多药耐药 (MDR) 主要是由MDR1基因编码的 P-糖蛋白的高表达引起的,该基因是一种 ATP 依赖性蛋白酶。在癌症中保持化学抗性细胞更强的侵袭和迁移能力也需要更多的 ATP 消耗。在这里,我们旨在通过减少细胞环境中的葡萄糖供应来逆转阻力。
方法:采用饥饿法逆转化学抗性,通过制备荧光葡聚糖纳米粒子来检测低糖培养细胞后化学抗性/化学敏感细胞混合物中化学抗性细胞的比例。
结果:与化学敏感细胞相比,化学抗性细胞具有更高的葡萄糖消耗、更高的 ATPase 表达和更强的葡萄糖依赖性。此外,在低葡萄糖条件下培养的癌细胞降低了化学抗性细胞的比例。
结论:饥饿疗法可作为逆转癌症耐药性的新方法。

关键词:癌症耐药性,P-糖蛋白,饥饿疗法,纳米颗粒,耐药性逆转
更新日期:2020-11-21
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