The Mechanism of Apoptosis induced by Hyperthermia combined with Chemotherapy inhibiting DNA Damage Repair in Hepatocellular Carcinoma Cells
Hyperthermia can play a synergistic role with chemotherapy in clinical practice.However,the underlying mechanism has not been fully illuminated yet.In this study,we explored the molecular mechanism of hyperthermia in combination with cisplatin(CDDP)in promoting cancer cell death.Under the optimal condition,we found that combination therapy resulted in the accumulation and activation of caspase-8,which is accompanied by increased activation of caspase-3,increased cell apoptosis,and decreased cell viability.Further investigation showed that CUL3 as E3 ligase is related to the ubiquitination accumulation of caspase-8 through K63-linked.In addition,our results showed that combination therapy induced DNA-PK degradation in HepG2 cells,inhibited the activity of DNA-PKcs and Ku80,inhibited DNA repair,improved the effect of CDDP.