Thermotherapy enhances oxaliplatin-induced cytotoxicity in human colon carcinoma cells

AIM:To observe the synergistic effects of hyperthermia in oxaliplatin-induced cytotoxicity in human colon adenocarcinoma Lovo cells.METHODS:The human colon adenocarcinoma cell line Lovo was obtained from Sun Yat-Sen University.Cells were sealed with parafilm and placed in a circulating water bath,and was maintained within 0.01 ℃ of the desired temperature (37 ℃,39 ℃,41 ℃,43 ℃ and 45 ℃).Thermal therapy was given alone to the negative control group while oxaliplatin was administered to the treatment group at doses of 12.5 μg/mL and 50 μg/mL.Identification of morphological changes,3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,flow cytometry and Western blotting were used to investigate the effect of thermochemotherapy on human colon adenocarcinoma Lovo cells,including changes in the signal pathway related to apoptosis.RESULTS:A temperature-dependent inhibition of cell growth was observed after oxaliplatin exposure,while a synergistic interaction was detected preferentially with sequential combination.Thermochemotherapy changed the morphology of Lovo cells,increased the inhibition rate of the Lovo cells (P < 0.05) and enhanced cellular population in the G 0 /G 1 phase (16.7% ± 4.8 % in phase S plus 3.7% ± 2.4 % in phase G 2 /M,P < 0.05).Thermochemotherapy increased apoptosis through upregulating p53,Bax and downregulating Bcl-2.Protein levels were elevated in p53,Bax/Bcl-2 in thermochemotherapy group as compared with the control group (P < 0.05).CONCLUSION:Thermochemotherapy may play an important role in apoptosis via the activation of p53,Bax and the repression of Bcl-2 in Lovo cells.