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