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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
DOI https://doi.org/10.2147/OTT.S181792
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Justinn Cochran
Peer reviewer comments 2
Editor who approved publication: Dr Tohru Yamada
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
