Hyperthermia improves cisplatin sensitivity in mismatch repair proficient colon cancer cell lines

SOTTILE M.L.; CUELLO CARRIÓN F.D.; VARGAS ROIG L.M.; CIOCCA D.R.; NADIN S.B.

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Introduction. HSPB1 (HSP27) and HSPA1A (HSP72) have been implicated in resistance to antineoplasic drugs, eg cisplatin (cPt) and they have also been associated with DNA repair. Hyperthermia (H) is used in combination with chemotherapy to improve the oncology treatment. cPt induced-DNA damage is recognized by the Mismatch Repair system (MMR), ie hMLH1 and hMSH2 proteins. However, the effects of hyperthermia in cPt sensitivity have not been determined in MMR deficient/proficient tumor cell lines. Objective. To determine the effect of hyperthermia on cPt sensitivity in HCT116 and HCT116+ch2 (MMR deficient) and HCT116+ch3 (MMR proficient) cell lines. Methodology. Cells were exposed to cPt (1 hour)  and H+cPt and collected at 0, 4 and 24 h after cPt. We used: RT-qPCR, alkaline comet assay, cytochemical detection of SA-beta gal activity, TUNEL and western blot. Results. cPt reduced the expression of HSPB1 in HCT116+ch3 cells (P<0.001). 24 h after cPt, heat shocked HCT116+ch3 cells (HS+cPt) showed increased expression of HSF1 (P<0.001) and hMLH1 (P<0.001). Hyperthermia reduced 30% cPt crosslinks (P<0.001) and increased senescence and apoptosis in HCT116+ch3 cells. Conclusions. A mild heat shock before cPt exposure increased senescence and apoptosis in MMR proficient cells, which may suggest that hyperthermia improves cisplatin sensitivity in human colon cancer cells.