Hyperthermia Enhance Sensitivity Of Pancreatic Adenocarcinoma Cell To Gemcitabine

Pancreatic cancer remains one of the most aggressive tumours with a 5-year survival rate of less than 5%.The dismal prognosis of this tumour entity that is associated.With a high degree of drug resistance has not changed over the past decades.Since 1997,gemcitabine-based regimens have been the therapy of choice for advanced pancreatic cancer.Yet the problem of increasing tumor resistance and lacking of new effective drugs is still tough.Presently,the clinical application of thermal therapy to improve the anti-cancer effect of gemcitabine empirically,but the specific mechanism is unclear.Here,we determined the changes of temperature,which 43℃,not 41℃ or 45℃,can significantly improve the sensitivity of pancreatic cancer cells to gemcitabine.43℃ hyperthermia in combination with gemcitabine treatment of pancreatic cancer cells can inhibit PANC-1 proliferation,migration and promote cell apoptosis,also can change the cell cycle distribution.In addition,intracellular reactive oxygen species(ROS)concentrate is significantly increased after treatment of 43℃ combined gemcitabine in PANC-1,and the mitochondrial membrane potential is reduced.High levels of intracellular ROS is recognized as one of the major causes of cancer cell apoptosis and has been developed into a promising therapeutic strategy for cancer therapy.The combination of 43℃ and gemcitabine was proved to induce ROS-mediated PANC-1 cell apoptosis in mitochondrial pathway by modulating the expression of Bax/Bcl-2.Our findings not only provided new insights into the anticancer effects of 43℃ hyperthermia and gemcitabine,but also highlighted the concemtration of intracellular ROS and subsequent mitochondrial apoptosis,and the increase of intracellular active metabolite of gemcitabine as possible mechanisms of hyperthermia enhance cytotoxicity of gemcitabine treated to pancreatic cancer cell.