Functions of the AP-2α gene in activating apoptosis and inhibiting proliferation of gastric cancer cells both in vitro and in vivo

Changqing Zeng; Zhimin Liu; Jian Zhang; Hongwei Fang; Cheng Fang; Yueming Wang; Sharvesh Raj Seeruttun; Jun Chen; Liangxiang Huang; Wei Wang

doi:10.5114/aoms.2017.71064

Functions of the AP-2α gene in activating apoptosis and inhibiting proliferation of gastric cancer cells both in vitro and in vivo

Arch Med Sci. 2017 Oct;13(6):1255-1261. doi: 10.5114/aoms.2017.71064. Epub 2017 Oct 31.

Authors

Changqing Zeng^{1

2}, Zhimin Liu^{1

2}, Jian Zhang³, Hongwei Fang⁴, Cheng Fang^{1

2}, Yueming Wang⁵, Sharvesh Raj Seeruttun^{1

2}, Jun Chen⁶, Liangxiang Huang², Wei Wang^{1

2}

Affiliations

¹ Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
² Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China.
³ Department of Gastrointestinal Surgery, Hangzhou First People's Hospital, Nanjing Medical University Affiliated Hangzhou Hospital, Hangzhou, China.
⁴ Department of Pain Management, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
⁶ Department of Orthopedic Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Abstract

Introduction: This study was designed to investigate the potential function of the activating protein 2α (AP-2α) gene in controlling the proliferation and apoptosis of gastric cancer.

Material and methods: Gastric cancer cell line MCG-803 cells and normal cell line GES-1 cells were selected to transfect pcDNA3.1(+)-AP-2α and pcDNA3.1(+) plasmids, respectively. Both mRNA and protein levels of AP-2α in each group transfected with the pcDNA3.1(+)-AP-2α plasmids were up-regulated after 48 h by real-time PCR and Western blotting analysis, leading to marked proliferation inhibition and significant cell cycle arrest.

Results: pcDNA3.1(+)-AP-2α reduced tumor tissue growth in a subcutaneous tumor gastric carcinoma nude mouse model. Protein over-expression of AP-2α in the nude mouse model was accompanied by down-regulation of Blc-2 and ErbB2, resulting in the up-regulation of caspase-3, -8, and -9, ERα and p21^WAF1/CIP1.

Conclusions: The reintroduction of the AP-2α gene by pcDNA3.1 could inhibit gastric tumor growth in vitro and in vivo, which may be an alternative future therapeutic molecular target for human gastric cancer.

Keywords: activating protein 2α; gastric cancer; gene therapy.