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Issue 8, 2018
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Regulating the Golgi apparatus by co-delivery of a COX-2 inhibitor and Brefeldin A for suppression of tumor metastasis

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Abstract

Finding a cure for breast cancer currently remains a medical challenge in due to the failure of common treatment methods to inhibit invasion and metastasis of cancer cells, which eventually leads to recurrence of breast cancer. Many secreted proteins are overexpressed and play crucial roles in tumorigenesis and development. The Golgi apparatus is a key protein processing and secretion factory in which metastasis-associated proteins are modified, transported and secreted; thus, regulating the Golgi apparatus of tumor cells is a viable strategy to inhibit tumor metastasis. Herein, celecoxib (CLX) and Brefeldin A (BFA) were encapsulated into the biocompatible polymer PLGA-PEG to form nanoparticles that act on the Golgi apparatus to treat metastatic breast cancer; CLX is a specific COX-2 inhibitor which accumulates in the Golgi apparatus, and BFA is a protein transport inhibitor fusing the Golgi apparatus into endoplasmic reticulum. The optimized CLX and BFA co-loaded nanoparticles (CBNPs) possessed good physicochemical properties. CBNPs efficiently damaged the Golgi apparatus within 30 min and showed enhanced cytotoxicity of CLX and BFA toward murine metastatic breast cancer 4T1 cells. The migration and invasion abilities of the cells were dramatically suppressed by the CBNPs. Further, the expression and secretion of metastasis-associated proteins such as matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) were remarkably decreased. Our findings showed that co-delivering CLX and BFA to regulate the Golgi apparatus may be an efficient strategy to inhibit breast cancer growth and suppress tumor cell metastasis.

Graphical abstract: Regulating the Golgi apparatus by co-delivery of a COX-2 inhibitor and Brefeldin A for suppression of tumor metastasis

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Publication details

The article was received on 03 Apr 2018, accepted on 26 May 2018 and first published on 06 Jun 2018


Article type: Paper
DOI: 10.1039/C8BM00381E
Citation: Biomater. Sci., 2018,6, 2144-2155
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    Regulating the Golgi apparatus by co-delivery of a COX-2 inhibitor and Brefeldin A for suppression of tumor metastasis

    R. Yu, L. Xing, P. Cui, J. Qiao, Y. He, X. Chang, T. Zhou, Q. Jin, H. Jiang and Y. Xiao, Biomater. Sci., 2018, 6, 2144
    DOI: 10.1039/C8BM00381E

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