Induction of Apoptosis by a Combination of Paclitaxel and Carboplatin in the Presence of Hyperthermia

Purpose: To study enhancing effects of paclitaxel in the thermochemotherapy of osteosarcoma cell lines and related mechanisms. Materials and Methods: Paclitaxel and carboplatin were used alone or jointly on OS732 cell lines in the presence of hyperthermia. Inhibition of proliferation was measured by MTT assay and cellular changes were assessed with inverted phase contrast and fluorescence microscopy. Apoptosis was analyzed with flow cytometry (FCM) and Fas expression by immunocytochemistry. Results: At 43 degrees C, one hour after the application of 10ug/ml paclitaxel and 5 mu g/ml carboplatin on OS732 cells jointly, the survival rate was 15.8% which was significantly lower than with 10 mu g/ml paclitaxel (45.8%) and 5 mu g/ml carboplatin (47.7%) respectively (P < 0.01). Moreover, changes of morphology and apoptotic rates indicated that the apoptosis-inducing effect of combined application was also much enhanced, as evident also regarding Fas expression. Conclusion: Paclitaxel is conducive to thermochemotherapy of osteosarcoma cell lines, possibly accomplished by up-regulation of Fas expression with induction of apoptosis.