Document Type : Research Paper

Authors

• Mahsa Ghiasian Abyaneh ¹
• Sorour Ramezanpour ²
• Somayeh Ehtesham ³

¹ Department of Biology, Parand Branch, Islamic Azad University, Parand Iran

² Faculty of Chemistry, K. N. Toosi University of Technology

³ Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran

Abstract

Anti-angiogenic agents improve the effect of cytotoxic drugs. In this study, the effect and mechanism of anti-cancer activity of an anti-angiogenic peptide, which specifically binds to VEGFR1 and VEGFR2 receptors and suppresses their signaling pathway, is investigated as a combination treatment with paclitaxel. The tumor model was breast carcinoma induced by a murine 4T1 cell line. Tumor-bearing mice were treated intravenously with paclitaxel, paclitaxel plus peptide (called VGB3), and PBS as a control from the fourteenth to the thirtieth days after tumor implantation (n=6). As a result of the treatments, paclitaxel effectively inhibited the growth of tumors, and the inhibition improved in the combination treatment with paclitaxel and peptide. Investigating the mechanism of action of treatments by immunohistochemistry and using antibodies against Ki67 (tumor cell proliferation marker), Cyclin D1 and CDK4 (cell cycle markers), P53 and Bcl2 (apoptotic markers) and E-Cadherin and Vimentin (metastasis markers) showed that, in tumor tissues, combined treatment more effectively inhibited the proliferation and the cell cycle of tumor cells, induced apoptosis and reduced the metastatic potential. According to these results, the combined treatment with the chemotherapy drug paclitaxel and anti-angiogenic peptide is more effective than the treatment with the chemotherapy drug alone, and the improvement of the potency of the combination therapy is related to inhibiting the proliferation, cell cycle arrest, apoptosis induction, and inhibiting metastasis in the tumor.

Keywords

• Breast cancer
• Anti-angiogenic peptide
• Paclitaxel
• Cell cycle
• Apoptosis

Main Subjects

• Biochemistry