Therapeutic Efficacy of Metronomic Doxorubicin and Low Dose of Gamma Radiation on Breast Cancer Model.

Abstract

Breast cancer is the most common malignancy in females internationally. Doxorubicin (DOX) has been well-thought-out as the most effective regimen for breast cancer treatment for several years. The chronic side effects of DOX obligate us to control the dosage that can be used, although its efficacy. Radiotherapy is a vigorous regimen in breast cancer treatment, but correlated side effects are determining factors for a successful recovery. Combined metronomic chemotherapy and radiotherapy, at low doses, can reduce the side effects of single-modality treatments. We have studied the dose 1.8 mg/kg twice per week for 8 weeks of DOX singly or with 0.5 Gy fractionated doses of gamma radiation on inducing cell death, cell cycle arrest, and apoptosis, and also P53, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), and caspase-3 gene expression in an animal breast cancer model. Treatment with DOX resulted in upregulation of apoptosis and downregulation of cell division at an accumulated dose of 0.5 Gy, as well as downregulation of Bcl-2 gene expression and upregulation of p53, Bax, and caspase-3 gene expression in animals bearing breast cancer. In addition, DOX in combination with radiation decreased the tumor size. A metronomic dose of DOX, when used with a low dose of gamma radiation, with the least side effects, could be a successful treatment for breast cancer in clinical trials.