Oncotarget

Research Papers:

The anti-ErbB2 antibody H2-18 and the pan-PI3K inhibitor GDC-0941 effectively inhibit trastuzumab-resistant ErbB2-overexpressing breast cancer

Lingfei Wang, Xiaojie Yu, Chao Wang, Shujun Pan, Beibei Liang, Yajun Zhang, Xiaodan Chong, Yanchun Meng, Jian Dong, Yirong Zhao, Yang Yang, Huajing Wang, Jie Gao, Huafeng Wei, Jian Zhao, Hao Wang, Chaohua Hu _, Wenze Xiao and Bohua Li

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:52877-52888. https://doi.org/10.18632/oncotarget.17907

Metrics: PDF 1281 views  |   HTML 1610 views  |   ?  


Abstract

Lingfei Wang1,2,*, Xiaojie Yu2,*, Chao Wang2,*, Shujun Pan3,*, Beibei Liang1, Yajun Zhang2, Xiaodan Chong2, Yanchun Meng4, Jian Dong5, Yirong Zhao2, Yang Yang2, Huajing Wang2, Jie Gao6, Huafeng Wei1,2, Jian Zhao1,2, Hao Wang2, Chaohua Hu7, Wenze Xiao8 and Bohua Li1,2

1Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China

2International Joint Cancer Institute, Second Military Medical University, Shanghai 200433, China

3Hangzhou Sanatorium of People’s Liberation Army, Hangzhou 310007, China

4Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai 200032, China

5Department of Vascular Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

6Department of Pharmaceutical Sciences, Second Military Medical University, Shanghai 200433, China

7Department of General Surgery, Xiaogan Central Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 432000, China

8Department of Rheumatology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China

*These authors contributed equally to this work

Correspondence to:

Chaohua Hu, email: huchaohua2006@126.com

Wenze Xiao, email: wenzexiao@yahoo.com

Bohua Li, email: bohuali1020@163.com

Keywords: trastuzumab resistance, GDC-0941, anti-ErbB2 antibody, programmed cell death, breast cancer

Received: March 07, 2017     Accepted: May 05, 2017     Published: May 16, 2017

ABSTRACT

Trastuzumab, an anti-ErbB2 humanized antibody, brings benefit to patients with ErbB2-amplified metastatic breast cancers. However, the resistance to trastuzumab is common. Our previously reported H2-18, an anti-ErbB2 antibody, potently induced programmed cell death in trastuzumab-resistant breast cancer cells. Here, we aim to investigate the antitumor efficacy of H2-18 in combination with the pan-PI3K inhibitor GDC-0941 in trastuzumab-resistant breast cancer cell lines. The results showed that H2-18 and GDC-0941 synergistically inhibited the in vitro proliferation of BT-474, SKBR-3, HCC-1954 and HCC-1419 breast cancer cells. H2-18 plus GDC-0941 showed significantly enhanced programmed cell death-inducing activity compared with each drug used alone. The combination of H2-18 and GDC-0941 did not increase the effect of single agent on ROS production, cell cycle and ErbB2 signaling. Importantly, the in vivo antitumor efficacy of H2-18 plus GDC-0941 was superior to that of single agent. Thus, the enhanced in vivo antitumor efficacy of H2-18 plus GDC-0941 may mainly be attributable to its increased programmed cell death-inducing activity. Collectively, H2-18 plus GDC-0941 could effectively inhibit tumor growth, suggesting the potential to be translated into clinic as an efficient strategy for ErbB2-overexpressing breast cancers.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 17907