Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma

摘要: Autophagy is a lysosome-dependent degradative pathway frequently activated in tumor cells treated with chemotherapy or radiation. Whether autophagy observed cancer represents mechanism that allows to survive therapy for initiating nonapoptotic form of programmed cell death remains controversial. To address this issue, the role Myc-induced model lymphoma generated from derived p53ERTAM/p53ERTAM mice (with ER denoting estrogen receptor) was examined. Such tumors are resistant apoptosis due lack nuclear p53. Systemic administration tamoxifen led p53 activation and regression followed by recurrence. Activation associated rapid appearance apoptotic induction surviving cells. Inhibition either chloroquine ATG5 short hairpin RNA (shRNA) enhanced ability alkylating drug induce death. These studies provide evidence serves as survival activators rationale use inhibitors such combination therapies designed human cancers.