Xiaogang Yan1, Yongfeng Hui2, Yongqiang Hua3, Liya Huang4, Libin Wang5, Fei Peng6, Chaofeng Tang2, Di Liu2, Jianjun Song2, Feng Wang7. 1. Department of Surgical Oncology, The First People's Hospital of Yinchuan, Yinchuan 750010, China. 2. Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750001, China. 3. Minimally Invasive Treatment Center, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. 4. Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan 750001, China. 5. Department of Beijing National Biochip Research Center Sub-center in Ningxia, General Hospital of Ningxia Medical University, Yinchuan 750001, China. 6. Ningxia Medical University, Yinchuan 750001, China. 7. Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan 750001, China. Electronic address: ku7bin@163.com.
Abstract
OBJECTIVE: Pancreatic carcinoma (PC), one of the most prevalent and malignant tumors, has a poor prognosis and a high mortality rate. EG-VEGF, a vascular endothelial growth factor from endocrine glands, also termed as PROK1, has a high positive expression rate in PC tissues and is involved in the pathogenesis of various tumors. However, the expression and potential role of EG-VEGF in PC has not been thoroughly explored. The aim of this study was to better clarify the expression and potential role of EG-VEGF in pancreatic carcinoma. METHODS: Immunohistochemical staining, western blotting, and RT-qPCR analysis were performed to detect the EG-VEGF level in PC tissues and cells. Subsequently, two short hairpin RNA (shRNA) lentiviral expression vector, shPROK1-1/shPROK1-2, were transfected into PANC-1 and BxPC-3 PC cell lines. MTT assay was used to determine cell proliferation. Meanwhile, flow cytometry assay was conducted to measure cell cycle and cell apoptosis. The protein levels of PI3K/AKT/mTOR pathway-related genes were also determined by western blotting. RESULTS: EG-VEGF was aberrantly expressed in PC samples, as compared with paracancerous samples. Knockdown of PROK1 notably decreased the protein level of EG-VEGF, indicating a successful downregulation model of EG-VEGF. EG-VEGF silencing remarkably attenuated cell proliferation, while also induced G0/G1 arrest and magnified the extent of cell apoptosis. Further, EG-VEGF knockdown significantly inhibited PI3K/AKT/mTOR signaling pathway by downregulating p-PI3K, p-AKT, and p-mTOR levels. CONCLUSION: This study identified the high-expression of EG-VEGF in pancreatic carcinoma tissues and cells, and demonstrated that EG-VEGF silencing inhibits the proliferation of PC cells and promotes apoptosis via regulating PI3K/AKT/mTOR pathway. Thus, EG-VEGF may become an essential target for the therapy of pancreatic cancer in the future.
OBJECTIVE:Pancreatic carcinoma (PC), one of the most prevalent and malignant tumors, has a poor prognosis and a high mortality rate. EG-VEGF, a vascular endothelial growth factor from endocrine glands, also termed as PROK1, has a high positive expression rate in PC tissues and is involved in the pathogenesis of various tumors. However, the expression and potential role of EG-VEGF in PC has not been thoroughly explored. The aim of this study was to better clarify the expression and potential role of EG-VEGF in pancreatic carcinoma. METHODS: Immunohistochemical staining, western blotting, and RT-qPCR analysis were performed to detect the EG-VEGF level in PC tissues and cells. Subsequently, two short hairpin RNA (shRNA) lentiviral expression vector, shPROK1-1/shPROK1-2, were transfected into PANC-1 and BxPC-3 PC cell lines. MTT assay was used to determine cell proliferation. Meanwhile, flow cytometry assay was conducted to measure cell cycle and cell apoptosis. The protein levels of PI3K/AKT/mTOR pathway-related genes were also determined by western blotting. RESULTS:EG-VEGF was aberrantly expressed in PC samples, as compared with paracancerous samples. Knockdown of PROK1 notably decreased the protein level of EG-VEGF, indicating a successful downregulation model of EG-VEGF. EG-VEGF silencing remarkably attenuated cell proliferation, while also induced G0/G1 arrest and magnified the extent of cell apoptosis. Further, EG-VEGF knockdown significantly inhibited PI3K/AKT/mTOR signaling pathway by downregulating p-PI3K, p-AKT, and p-mTOR levels. CONCLUSION: This study identified the high-expression of EG-VEGF in pancreatic carcinoma tissues and cells, and demonstrated that EG-VEGF silencing inhibits the proliferation of PC cells and promotes apoptosis via regulating PI3K/AKT/mTOR pathway. Thus, EG-VEGF may become an essential target for the therapy of pancreatic cancer in the future.