Improved Therapeutic Efficacy of Doxorubicin Chemotherapy with Cannabidiol in 4T1 Mice Breast Cancer Model

Abstract

Abstract Background Breast cancer is one of the world’s most frequently diagnosed malignancy and the second highest cause of all cancers in females. This cancer mortality is mostly due to lung metastasis. High dose chemotherapy is one of therapeutic strategies beside others. Doxorubicin (DOX) is a widely used chemotherapy agent. however, use of DOX is limited due to its dose- depended cardiotoxic effects. Recently, cannabidiol (CBD) shows anti-tumoral and cardioprotective effects so we aimed to CBD administration with high-dose DOX chemotherapy can improve anticancer effect and reduce cardiotoxicity side effect. Method Mice breast cancer model established by injecting 4T1 cell lines. One group did not injected by 4T1 cells as a not cancerous group and administrated normal saline (1ml). In cancerous groups one group consider as cancerous control and administrated normal saline (1ml), other one administrated only DOX (5 mg/kg, IV) on day 1,7,14, other administrated CBD (5 mg/kg, IP) as DOX schedule, nex group administrated CBD and DOX at same time with previews doses and schedule, the last one administrated CBD one day before DOX as pretreatment. On day 21 all mice sacrificed, heart and lungs obtained and histological section preformed. SOD2, iNOS, MMP2, MMP9 evaluated through western blot and TUNEL test preformed for breast tumor. Results TUNEL test demonstrated CBD + DOX and pretreatment group was significantly green even compare to DOX group (P < 0.05). In CBD + DOX SOD2 increased and iNOS, MM2 and MMP9 decreased. Conclusions This study shows CBD + DOX at same time can increase anti-tumoral effect and reduce DOX cardiotoxicity effect. However CBD alone had a cardioroxic effect.