Increased Autophagy Levels Mediate Cisplatin Resistance in Cisplatin-Resistant Cells While Also Rendering Them Vulnerable to Autophagy Induction

摘要: Autophagy plays an important role in tumor development because of its capacity to maintain energy homeostasis by recycling damaged intracellular proteins and organelles, increased autophagy levels are reported mediate drug resistance many cancers. However, whether high negatively impact cell growth is unknown. Herein, we found that cisplatin (ddp)-resistant cells were more sensitive glutamine (Gln) deprivation than ddp-sensitive cells, they showed significant G1 arrest apoptosis rates under Gln-deficient conditions. Furthermore, ddp-resistant had a higher level autophagy, which mediated ddp resistance. Further analysis indicated Gln deficiency could trigger enhancing activation the signaling pathway AMPK/ULK1 due their basal level. Interestingly, rapamycin, rapamycin efficiently suppress vivo. Taken together, our study demonstrated became vulnerable for first time, suppressing via induction was possible with treatment.