Imatinib enhances the anti-tumour effect of doxorubicin in canine B-cell lymphoma cell line

Abstract

Canine lymphoma is one of the most common malignant tumours occurring in dogs and has a high incidence worldwide. Despite advances in cancer prevention, the treatment of neoplastic diseases still requires improvement. Some cancer cells may resist the effect of chemotherapeutic agents by up-regulating drug transporters leading to increased drug efflux, resulting in intrinsic or acquired drug resistance, which is a mechanism commonly seen in doxorubicin-resistant tumour cells. In this study, canine B-cell lymphoma cell line CLBL1-8.0, a doxorubicin-resistant B cell lymphoma cell line derived from CLBL-1 by increasing the doxorubicin concentration during culturing, exhibited high expression of P-glycoprotein (P-gp, ATP-binding cassette sub-family B member 1 [ABCB1]). These proteins are commonly involved in cancer cell resistance to doxorubicin.Imatinib, a tyrosine kinase inhibitor significantly potentiated the sensitivity of doxorubicin in P-gp-overexpressing doxorubicin-resistant cells. Moreover, a combination of these two drugs may increase the retention of doxorubicin by decreasing the efflux of doxorubicin without affecting P-gp protein overexpression. In conclusion, imatinib reversed doxorubicin resistance by decreasing drug efflux in P-gp-overexpressing doxorubicin-resistant canine lymphoma cells. These results suggest that combining doxorubicin, one of the most widely used chemotherapeutic drugs in the treatment of canine lymphoma, with imatinib might potentially overcome doxorubicin resistance in a clinical setting.