Oncotarget

Research Papers:

CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells

Lijuan Xiong, Li Ding, Haoyong Ning, Chenglin Wu, Kaifei Fu, Yuxiao Wang, Yan Zhang, Yan Liu and Lijun Zhou _

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Oncotarget. 2016; 7:57737-57751. https://doi.org/10.18632/oncotarget.10252

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Abstract

Lijuan Xiong1,*, Li Ding2,*, Haoyong Ning3,*, Chenglin Wu1, Kaifei Fu1, Yuxiao Wang1, Yan Zhang4, Yan Liu2, Lijun Zhou1

1Central Laboratory, Navy General Hospital, Beijing 100048, P.R. China

2The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510630, P.R.China

3Department of Pathology, Navy General Hospital, Beijing 100048, P.R. China

4Department of Surgery, Navy General Hospital, Beijing 100048, P.R. China

*These authors equally contributed to this work

Correspondence to:

Lijun Zhou, e-mail: [email protected]

Keywords: CD147, HER2, breast cancer, antibody drug resistance/sensitivity, trastuzumab efficacy

Received: January 13, 2016    Accepted: May 04, 2016    Published: June 23, 2016

ABSTRACT

Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types of cancer cells. Whether CD147 alters the effect of trastuzumab on HER2-positive breast cancer cells has not been previously reported. Our study confirmed that CD147 suppression enhances the effects of trastuzumab both in vitro and in vivo. CD147 suppression increased the inhibitory rate of trastuzumab and cell apoptosis in SKBR3, BT474, HCC1954 and MDA-MB453 cells compared with the controls. Furthermore, CD147 knockdown increased expression of cleaved Caspase-3/9 and poly (ADP-ribose) polymerase (PARP) and decreased both mitogen-activated protein kinase (MAPK) and Akt phosphorylation in the four cell lines. In an HCC1954 xenograft model, trastuzumab achieved greater suppression of tumor growth in the CD147-knockdown group than in the shRNA negative control (NC) group. These data indicated that enhancement of the effect of trastuzumab on HER2-positive cells following CD147 knockdown might be attributed to increased apoptosis and decreased phosphorylation of signaling proteins. CD147 may be a key protein for enhancing the clinical efficacy of trastuzumab.


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