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Inhibition of cancer cell migration with CuS@mSiO2-PEG nanoparticles by repressing MMP-2/MMP-9 expression

Authors Deng G, Zhou F, Wu Z, Zhang F, Niu K, Kang Y, Liu X, Wang Q, Wang Y, Wang Q

Received 7 August 2017

Accepted for publication 17 September 2017

Published 21 December 2017 Volume 2018:13 Pages 103—116


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun

Guoying Deng,1,* Feng Zhou,1,* Zizheng Wu,2–4 Fei Zhang,1 Kerun Niu,2,3 Yingjie Kang,5 Xijian Liu,6 Qiugen Wang,1 Yin Wang,7 Qian Wang1

1Trauma Center, 2Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 3Department of Orthopaedics, Shanghai General Hospital of Nanjing Medical University, 4Department of Orthopaedics, Baoshan Branch of Shanghai General Hospital of Shanghai Jiaotong University, 5Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 6College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 7Ultrasound Department of Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Abstract: The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a trans­well migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic.

Keywords: metastasis inhibition, photothermal nanoparticles, SRC/FAK signaling pathway, survival curves, MMPs

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