INDUCTION OF HSP70 IS ASSOCIATED WITH VINCRISTINE RESISTANCE IN HEAT-SHOCKED 9L RAT-BRAIN TUMOR-CELLS

The most prominent cellular changes in heat-shock response are induction of HSPs synthesis and reorganisation of cytoskeleton. Vincristine was used as a tool to evaluate the integrity of microtubules in 9L rat brain tumour cells recovering from heat-shock treatment. Cells treated at 45-degrees-C for 15 min and recovered under normal growing condition became resistant to vincristine-inflicted cytotoxicity and microtubule destruction. Among all HSPs, the level of HSP70 and the degree of vincristine resistance are best correlated. HSP70 and tubulin were found to be associated with each other as they were co-immunoprecipitated by either anti-HSP70 or anti-beta-tubulin monoclonal antibody. The current studies establish for the first time that HSP70 can complex with tubulin in cells and this association may stabilise the organisation of microtubules thus protect the heat-treated cells from vincristine damage. These findings are noteworthy in combining hyperthermia and chemotherapy in the management of malignant diseases.