Heat shock modulators protecting normal cells during chemotherapy

Abstract

Chemotherapy is known to cause a vast spectrum of side effects including myelosuppression. Although much research is being carried out to find more specific treatments which could reduce the side effects, chemotherapies such as cisplatin are still being used. Screening 5 different chemotherapies (cisplatin, cytarabine, doxorubicin, methotrexate and vincristine), XTT analysis was carried out to determine the IC50 on a variety of cell lines corresponding to tumours which are currently being treated by the chemotherapies tested, and also on a bone marrow model. Tex-OE®, both with and without heat shock, was included as a pre-treatment and the new IC50 values determined. Animal models were then used to determine the in vivo effect of Tex-OE® pre-treatment with cisplatin. Colony assays were used to determine the viability of the animal bone marrows collected. Tex-OE® pre-treatment was found to increase the cell viability of the bone marrow model (cell viability increase by up to 80 % when compared to treatment with 4 µg/mL cisplatin alone (p < 0.05)) while further decreasing the cell viability of the cancer cell lines tested when compared to chemotherapy treatment alone. Heat shock is known to increase the effect of the chemotherapy on tumour cells, but the effects observed in this study exceeded those from other studies using heat shock, while the effects in this study were also observed without the inclusion of heat shock. An increase in the number of colonies formed (from 20.5 in the cisplatin-treated group to 25.375, 31.9 and 23.25 for the groups receiving cisplatin together with TEX-OE® at concentrations of 50, 100 and 200 µg/mL respectively) was observed from the bone marrows of the individuals who Wf!rf! giwm Tex-OE® pre-treatment which exceeded that of the control group of individuals (i.e. received no treatment; with an average of 25.6 colonies). The findings suggest that Tex-OE® pre-treatment is effective at reducing. and in some cases even eliminating. the myelosuppressive effects of the cisplatin treatment while possibly increasing the efficacy of the treatment on the tumours.