Oncotarget

Research Papers:

AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

Xi Wei, Wei Duan, Ying Li, Sheng Zhang, Xiaojie Xin, Lei Sun, Ming Gao, Qing Li and Dong Wang _

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Oncotarget. 2016; 7:34430-34441. https://doi.org/10.18632/oncotarget.9119

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Abstract

Xi Wei1, Wei Duan2, Ying Li3, Sheng Zhang1, Xiaojie Xin1, Lei Sun4, Ming Gao5, Qing Li2, Dong Wang2

1Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin,China

2Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, China

3The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

4Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

5Department of Thyroid and Cervical Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin,China

Correspondence to:

Dong Wang, email: dongwang64@sina.com

Qing Li, email: likunze88824@163.com

Keywords: gastric cancer, AT101, APE1, 5-FU, Her-2 positive

Received: February 20, 2016     Accepted: April 11, 2016     Published: April 30, 2016

ABSTRACT

Gastric cancer remains a disease with a high mortality rate despite of multiple therapeutic strategies. So far, it is very important to develop new treatment approaches to improve current therapeutic efficacy in gastric cancer. Apurinic/apyrimidinic endonuclease (APE1) involves in DNA base excision repair (BER) during DNA damage pathway. APE1 was found to be associated with poor overall survival with gastric cancer patients. In the in vitro experiment, we tested APE1 inhibitor-AT101 could potently inhibit gastric cancer cell growth and further induce cancer cell apoptosis and autophagy through p53-dependent pathway. Downregulation of APE1 by AT101 has ability to suppress gastric cancer cell migration and renewal through inhibition of CD133, Nanog and LC3expression. Based on findings that Her-2 positive expression cases has poor prognosis from our dataset and TCGA database, we investigated the role of AT101 in synergetic efficacy with 5-FU treatment in Her-2 overexpression gastric cancer in vivo, indicating that AT101 is able to enhance 5-FU in the shrinkage of xenograft mice tumor and induction of cell apoptosis. In summary, the data obtained from our study showed APE1 is guided as a potential therapeutic target for gastric cancer. AT101 could be regarded as a potent inhibitor to promote chemotherapeutic sensitivity in patients with gastric cancer.


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