The synergistic effect of combination temozolomide and chloroquine treatment is dependent on autophagy formation and p53 status in glioma cells.

摘要: Abstract Temozolomide (TMZ) is an alkylating agent used for the treatment of glioblastoma. The late autophagy inhibitor chloroquine (CQ) inhibits glioblastoma tumors in a p53-independent and p53-dependent manner. We addressed possible beneficial effect combination with TMZ CQ by examining molecular cellular mechanism co-treatment. Combination U87 cell (wild type p53) synergistically reduced proliferation enhanced apoptosis, increased sub-G 1 hypodiploid cells caspase activation. This was abolished pan-caspase inhibitor, Z-VAD-FMK. induced autophagy, addition further autophagic vacuoles. Inhibition early stages Beclin knockdown 3-methyladenine pretreatment prevented treatment. also upregulated p53 phospho-p53 levels, whereas or overexpression mutant effect. In contrast, therapy had no on U373 (mutant apoptosis within 3 d, although co-treatment vacuole accumulation. However, long term 9–10 d effectively decreased clonal growth G 2 –M arrest. knockdown. Our data support glioma via differential autophagy-associated mechanisms, depending status.