Original Article
Low dose cyclophosphamide inhibiting the liver metastasis of colon cancer by regulating immunity
Xiaoming Huang, Nanrong Zhang, Yifeng Zou, Xiaosheng He, Xutao Lin, Ping Lan, Yunle Wan
Published 2017-12-01
Cite as Chin Arch Gen Surg(Electronic Edition), 2017, 11(6): 365-369. DOI: 10.3877/cma.j.issn.1674-0793.2017.06.002
Abstract
ObjectiveTo investigate the underlying mechanism of low-dose cyclophosphamide inhibiting the liver metastasis of colon cancer by regulating immunity.
MethodsThirty mice were randomly divided into five groups. After the establishment of liver metastasis in colon cancer models, mice in treatment groups were injected with low-dose cyclophosphamide (CTX, 20 mg/kg) at different time points. The liver and spleen tissues were examined for T cell markers via flow cytometry. IL-10 and TGF-β1 expression in liver tissues was analyzed by immunohistochemistry. Serum IFN-γ and IL-10 levels were detected by ELISA.
ResultsThis study showed that the expression of CD4+ T cells, CD8+ T cells, and IFN-γ were downregulated while the expression of IL-10 and TGF-β1 was upregulated in the liver metastasis of colon cancer in mice. Further, the local and systemic microenvironments of the liver were changed, leading to reduced antitumor immune responses and thus the liver metastasis. However, treatment with low-dose CTX could enhance antitumor immune response, inhibit the expression of IL-10 and TGF-β1, and induce secretion of IFN-γ.
ConclusionsLow-dose CTX exerts its antitumor activity by changing the systemic and local immune microenvironments and enhancing immune regulation in mice. CTX may be used as a drug for preventing/treating the liver metastasis of colon cancer.
Key words:
Colonic neoplasms; Cyclophosphamide; Neoplasm metastasis; Tumor microenvironment
Contributor Information
Xiaoming Huang
Department of Hepatobiliary Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, China
Nanrong Zhang
Department of Anesthesiology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, China
Yifeng Zou
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, China
Xiaosheng He
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, China
Xutao Lin
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, China
Department of Gastrointestinal Endoscopy, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, China
Ping Lan
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, China
Yunle Wan
Department of Hepatobiliary Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou 510655, China
