A comparison of low-dose cyclophosphamide treatment with artemisinin treatment in reducing the number of regulatory T cells in murine breast cancer model

作者：Langroudi Ladan^*; Hassan Zuhir Muhammad; Ebtekar Massoumeh; Mandavi Mehdi; Pakravan Nafise; Noori Shokoofe

来源：International Immunopharmacology, 2010, 10(9): 1055-1061.

DOI：10.1016/j.intimp.2010.06.005

• Artemisinin
• Breast cancer
• Regulatory T cells
• Cyclophosphamide

Background: Artemisinin (ART) is a sesquiterpene lactone. Possessing an endoperoxide bridge is unique among ant-imalarial drugs, and now much attention is focused on the anti-cancer properties of ART. In this study we aimed at the immunomodulatory effects of artemisinin in the treatment of breast cancer in comparison to the conventional anti-cancer drug, cyclophasphamide (CTX).
Methods: We examined delayed-type hypersensitivity, antibody and IL-4 and IFN gamma production, tumour volume, tumour infiltrated regulatory T cells (Treg) and spleen lymphocyte proliferation assay. Briefly three groups of five 4-6 week old female Balb/c tumour-bearing mice (mouse mammary tumour) were treated with 2.8 mg/kg ART and 20 mg/kg CTX intraperitoneally for 20 consecutive days. Tumour volume was measured using a digital vernier calliper (with accuracy of 0.01). Mice were sacrificed and percentage of tumour infiltrating Tregs were obtained using flow cytometry (BD, USA). Proliferation of splenocytes was obtained using BrdU proliferation assay (Roche).
Results: Our results showed that ART can reduce the number of Tregs in tumour stroma (P-value <= 0.047) as compared to CTX (P-value >= 0.05) and control. Furthermore ART increased IFN gamma/IL-4 ratio produced in splenocyte culture (P-value <= 0.001). Proliferation assay did not show any significant difference (P-value >= 0.05).
Discussion: Cancer is a multi-factorial disease which needs a multi-approach treatment. Early accumulation of Treg cells in the tumour tissue correlates with tumour progression and is an indication of bad prognosis. According to the obtained results, ART can reduce the number of Tregs. We suggest using artemisinin, with its dual action mechanism. It can effectively kill cancer cells along with reducing the suppressive microenvironment.

• 出版日期2010-9