Thermosensitivity of multidrug-resistant human gastric and pancreatic carcinoma cells

Often, tumour cells acquire drug resistance phenotypes, which include the c lassical multidrug resistance (MDR) phenomenon accompanied by the synthesis of the P-glycoprotein (Pgp) and atypical MDR phenotypes mediated by differ ent, in part unknown, mechanisms. To investigate the susceptibility of tumo ur cells exhibiting different kinds of MDR to treatment with heat, the hype rthermic survival of established human gastric and pancreatic carcinoma cel l lines were studied and sublines exhibiting a classical and an atypical MD R phenotype were derived, respectively. Arrhenius analysis of this panel of gastrointestinal tumour cells revealed that both the classical and the aty pical MDR variants exhibited no breaking points. (T*) in contrast to the pa rent tumour cells. The activation enthalpies E-A were about 40% lower at T > T* in comparison to the E-A at lower temperatures. Classical MDR variants of both gastrointestinal tumour cell types exhibited a similar E-A value, whereas the E-A of atypical MDR gastric carcinoma cells was 1.6-fold higher than the E-A of corresponding pancreatic carcinoma cells. In comparison to the parent lines, the drug resistant variants exhibited a 2.1-fold (gastri c carcinoma, classical MDR), 2.7-fold (gastric carcinoma, atypical MDR) and 1.4-fold (pancreatic carcinoma, classical MDR) increase of activation enth alpies and a nearby unchanged E-A in pancreatic carcinoma cells exhibiting an atypical MDR.