In Vitro and In Vivo Investigation of the Radiation-Sensitizing Effects of Melittin in Breast Cancer Cells

Abstract

Melittin, a major peptide constituent of bee venom, exhibits potential anticancer effects against various types of cancers, including breast cancer. We determined the radiosensitizing effects of melittin on breast cancer both in vitro and in vivo models. Viability of murine (4T1) and human (MCF-7) breast cancer cell lines treated with melittin was measured by MTT assay. The radiosensitizing effects of melittin were investigated using a clonogenic assay. The expression of apoptosis-related proteins was assessed by Western blotting. Tumor growth with/without melittin treatment was investigated in a 4T1 xenograft breast cancer mouse model. Melittin-mediated radiosensitivity was evaluated by assessing growth inhibitory activity based on the change in tumor volume and the time taken for a five-fold increase in the relative tumor volume (RTV5). Melittin inhibited the viability of 4T1 and MCF-7 breast cancer cells with IC50 of 1.70 and 1.51 mu M, respectively. Melittin decreased clonogenicity with a sensitization enhancement ratio of 1.09-1.32. Melittin plus irradiation significantly increased the Bax/Bcl-2 ratio. In vivo, intraperitoneal injection of melittin significantly reduced tumor growth in 4T1 tumor-bearing mice. Melittin plus irradiation treatment increased the tumor growth inhibition rate (87.97%) as compared with the control group and had the greatest effect on tumor growth inhibition with the longest RTV5 of 37.0 days. Irradiation alone, melittin alone, and control treatment showed RTV5 of 24.4, 16.2, and 13.6 days, respectively. By inducing apoptosis, melittin serves as a promising radiosensitizer for breast cancer radiotherapy, providing a valuable strategy to improve the efficacy of radiation therapy.