Effect of Starvation in Reversing Cancer Chemoresistance Based on Drug-Resistance Detection by Dextran Nanoparticles

Abstract

Chenglong Wang,1 Xuzhu Gao,1 Fanchen Wang,1 Wencai Guan,1 Hongjing Dou,2 Guoxiong Xu1 1Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai 201508, People’s Republic of China; 2The State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of ChinaCorrespondence: Guoxiong XuResearch Center for Clinical Medicine, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] DouThe State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: 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

Keywords

• cancer drug-resistance
• p-glycoprotein
• starvation therapy
• nanoparticles
• resistance reversal