GDF11 restrains tumor growth by promoting apoptosis in pancreatic cancer

Abstract

BackgroundGrowth 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.PurposeTo investigate the expression and significance of GDF11 in pancreatic cancer.Patients and methodsPancreatic 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.ResultsThe 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.ConclusionThese findings suggested that GDF11 acted as a tumor suppressor gene for pancreatic cancer.

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

“…In pancreatic cancer, mutation of TP53 at codon 249 can alter the structure of p53, thus affecting its binding to a specific region of DNA and enhancing the risk of cancer [ 46 , 47 ]. A study showed that GDF11 regulates the biological behaviors of pancreatic cancer cells to influence their differentiation and high expression of GDF11 is associated with favorable OS in pancreatic cancer [ 48 ]. RAF1 accelerates migration and invasion of pancreatic cancer and disorders of the RAF1 pathway are related to worse prognosis in pancreatic cancer patients [ 49 , 50 ].…”

Bioinformatics Network Analyses of Growth Differentiation Factor 11 Anti-aging Study

“…Liu et al also found that the PANC-1 cell line overexpressing GDF11 by lentivirus showed increased apoptosis when analyzed for the role of GDF11 in pancreatic cancer. At the same time, cells treated with RNAi reduced GDF11 showed decreased apoptosis 17 . Millet et al believe that the TGFβ family promotes apoptosis by binding to downstream SMAD2/3 and inhibiting bcl-2, an anti-apoptotic protein 18 .…”

Prognostic value of Glypican family genes in early-stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy and possible mechanisms

“…In pancreatic cancer, mutation of TP53 at codon 249 can alter the structure of protein p53, thus affecting its binding to speci c region of DNA and enhancing risk of the cancer (46,47). A study showed that GDF11 regulates the biological behaviors of pancreatic cancer cells to in uence their differentiation and high expression of GDF11 is associated with favorable OS for pancreatic cancer (48). RAF1 accelerates the migration and invasion of pancreatic cancer and disorder of RAF1 pathway is related to worse prognosis of pancreatic cancer patients (49,50).…”