Thermosensitivity of multidrug-resistant human gastric and pancreatic carcinoma cells.
Often, tumour cells acquire drug resistance phenotypes, which include the classical multidrug resistance (MDR) phenomenon accompanied by the synthesis of the P-glycoprotein (Pgp) and atypical MDR phenotypes mediated by different, in part unknown, mechanisms. To investigate the susceptibility of tumour cells exhibiting different kinds of MDR to treatment with heat, the hyperthermic survival of established human gastric and pancreatic carcinoma cell lines were studied and sublines exhibiting a classical and an atypical MDR phenotype were derived, respectively. Arrhenius analysis of this panel of gastrointestinal tumour cells revealed that both the classical and the atypical MDR variants exhibited no breaking points (T*) in contrast to the parent 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 (gastric carcinoma, classical MDR), 2.7-fold (gastric carcinoma, atypical MDR) and 1.4-fold (pancreatic carcinoma, classical MDR) increase of activation enthalpies and a nearby unchanged E(A) in pancreatic carcinoma cells exhibiting an atypical MDR.
Lage
H
H
Institute of Pathology, Humboldt University Berlin, Germany. hermann.lage@charite.de
Jordan
A
A
Scholz
R
R
Dietel
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival; D018432:Drug Resistance, Multiple / Q000235:genetics; D019450:Genes, MDR; D006801:Humans; D006979:Hyperthermia, Induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents