Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Serum amyloid P down-regulates CCL-1 expression, and inhibits Ras/MAPK signaling and development of breast cancer

Shuhong Ding¹, Hongzhi Li², Xiaohui Li³, Wenwen Wang¹, Xiuling Du¹, Guoying Dong¹, Ping Zhang¹

¹Department of Breast Diseases, Second Hospital of Shandong University, Jinan; ²Department of Emergency Surgery, Linyi Central Hospital, Linyi; ³Nursing Department, Second Hospital of Shandong University, Jinan, Shandong, China.

For correspondence:- Ping Zhang Email: pingzhang3117@163.com Tel:+8653185875374

Accepted: 14 August 2017 Published: 30 September 2017

Citation: Ding S, Li H, Li X, Wang W, Du X, Dong G, et al. Serum amyloid P down-regulates CCL-1 expression, and inhibits Ras/MAPK signaling and development of breast cancer. Trop J Pharm Res 2017; 16(9):2089-2095 doi: 10.4314/tjpr.v16i9.7

© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the role of serum amyloid component P (SAP) on Ras/MAPK pathway in the development of breast cancer (BC) via regulation of chemokine (CC motif) ligand 1 (CCL-1).

Methods: Breast cancer (BC) and metastasis models were established using SAP-Tg transgenic mice and WT C57BL/6 mice. The effect of SAP on growth and metastasis was observed. Differentially expressed proteins in SAP-Tg and C57BL/6 serum were analyzed, and further determined by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR). The effect of SAP on CCL1/Ras/MAPK signaling pathway was studied by immunoblotting.

Results: Compared with WT control, SAP-Tg BC model showed a significant reduction in tumor volume and prolonged survival (p < 0.05). In the lung metastasis model, SAP-Tg mice showed a decreased number of nodules on the organ surface (p < 0.05). Protein microarray screening results showed that SAP inhibited CCL-1 expression (p < 0.05). CCL-1 mRNA level in SAP-Tg mice was significantly lower than WT control (p < 0.05). After stimulating RAW cells (mouse macrophage line) with SAP recombinant protein, ELISA results showed that CCL-1 secretion significantly decreased (p < 0.05). In both models, P38 and ERK1/2 activation in SAP-Tg mice were significantly lower than that in C57BL/6 mice.

Conclusion: SAP inhibits the growth and metastasis of BC, possibly by reducing the secretion of CCL-1 and inhibiting Ras/MAPK signaling pathway, thus suggesting a possible treatment strategy for breast cancer.

Keywords: Serum amyloid component P (SAP), chemokine (CC motif) ligand 1 (CCL-1), Breast cancer, NF-_4;B, Ras/MAPK signaling pathway