GDF11 restrains tumor growth by promoting apoptosis in pancreatic cancer
Authors Liu Y, Shao L, Chen K, Wang Z, Wang J, Jing W, Hu M
Received 29 July 2018
Accepted for publication 9 October 2018
Published 27 November 2018 Volume 2018:11 Pages 8371—8379
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Tohru Yamada
Yanzhe Liu,1,* Lijuan Shao,2,* Kuang Chen,1 Zizheng Wang,1 Jin Wang,1 Wei Jing,3 Minggen Hu1
1Department of Hepatobiliary and Pancreatic Surgical Oncology, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen, People’s Republic of China; 3Department of General Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, People’s Republic of China
*These authors contributed equally to this work
Background: Growth differentiation factor (GDF) acted as a factor that regulated proliferation, apoptosis and differentiation in several tumors. However, the effects of growth differentiation factor (GDF11) in pancreatic cancer remain unclear.
Purpose: To investigate the expression and significance of GDF11 in pancreatic cancer.
Patients and methods: Pancreatic cancer and corresponding paracancerous tissues (n=28) were collected from the Department of Hepatobiliary and Pancreatic Surgical Oncology of Chinese PLA General Hospital. Tissue microarray was obtained from Outdo Biotech Co., Ltd. (Shanghai, People’s Republic of China). GDF11 mRNA and protein expressions in pancreatic cancer samples and cell lines were detected using qRT-PCR, Western-Blot and immunohistochemistry. Overexpression and knockdown of GDF11 were performed with lentiviral transduction system and siRNA technique in PANC-1 cell line and CFPAC-1 cell line. Proliferation, migration and invasion of pancreatic cancer cell lines were examinated by MTS and transwell assay, respectively. Flow cytometry was used for cell apoptosis analysis.
Results: The results of this study indicated that GDF11 was significantly down-regulated in pancreatic cancer tissues compared with adjacent tissues of pancreatic cancer. GDF11 was also associated with low expression in pancreatic cancer cell lines when compared with normal pancreatic cell line. In a cohort of 63 pancreatic cancer patients, high GDF11 expression levels was associated with favorable perineural invasion, T classification, N classification and overall survival (OS). Cox proportional hazards model revealed that high GDF11 expression was an independent predictor of favorable prognosis (HR: 0.496; 95% CI: 0.255–0.967; P=0.040). Overexpression of GDF11 in PANC-1 cells repressed the proliferation, migration and invasion abilities in vitro. Inhibition of GDF11 in CFPAC-1 showed inverse results. Furthermore, enhanced GDF11 expression promoted apoptosis and down-regulated GDF11 expression inhibited apoptosis in pancreatic cancer cell lines.
Conclusion: These findings suggested that GDF11 acted as a tumor suppressor gene for pancreatic cancer.
Keywords: GDF11, pancreatic cancer, proliferation, apoptosis, prognosis
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