Combined use of cyclophosphamide and Chalone 19-peptide in experimental breast cancer

Yuanxi Huang,^1,* Yan He,^2,* Shengqian Ye,² Xiaomei Li,¹ Qingqi Zhong,¹ Zhuo Chen,¹ Xiaoming Jin<sup>2

1</sup>Third Affiliated Hospital, ²Department of Pathology, Harbin Medical University, Harbin, Heilongjiang, People's Republic of China

*These authors contributed equally to this work

Background: Cyclophosphamide is a potent anticancer drug, but its clinical utility is limited because of its severe side effects, in particular liver damage. Chalone 19-peptide induces apoptosis of tumor cells and inhibits tumor growth. The present study investigated the antitumor effects of a combination of cyclophosphamide and Chalone 19-peptide in experimental breast cancer.
Methods: An animal model of breast cancer was developed, consisting of an MDA-MB-231 cell line implanted in the nude mouse. Eight doses of a combination of cyclophosphamide 50 mg/kg or 100 mg/kg and Chalone 19-peptide 6.6 mg/kg were administered, and the mice were euthanized 28 days after the final drug injection. Histopathologic analysis of tumor size, metastasis, and apoptosis of cancer cells was performed. Control mice were injected intraperitoneally with either cyclophosphamide alone or the same volume of solvent.
Results: Tumor sizes in the treatment groups were smaller than in the controls. No metastasis was found in the groups treated with cyclophosphamide and Chalone 19-peptide, but lung metastasis was found in controls. Liver damage in the groups treated with cyclophosphamide was more serious than in the other groups.
Conclusion: Addition of Chalone 19-peptide can improve the ability of cyclophosphamide to inhibit tumor growth and also reduces side effects.

Keywords: cyclophosphamide, Chalone 19-peptide, tumor suppression, apoptosis, hepatic injury