Neuropeptide Y1 receptor inhibits cell growth through inactivating mitogen-activated protein kinase signal pathway in human hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common cancers, and its incidence is increasing worldwide. Neuropeptide Y (NPY) broadly expressed in the central and peripheral nervous system. It participates in multiple physiological and pathological processes through specific receptors. Evidences are accumulating that NPY is involved in development and progression in neuro- or endocrine-related cancers. However, little is known about the potential roles and underlying mechanisms of NPY receptors in HCC. In this study, we analyzed the expression of NPY receptors by real-time polymerase chain reaction, Western blot, and immunohistochemical staining. Correlation between NPY1R levels and clinicopathological characteristics, and survival of HCC patients were explored, respectively. Cell proliferation was researched by CCK-8 in vitro, and tumor growth was studied by nude mice xenografts in vivo. We found that mRNA and protein level of NPY receptor Y1 subtype (NPY1R) significantly decreased in HCC tissues. Low expression of NPY1R closely correlated with poor prognosis in HCC patients. Proliferation of HCC cells was significantly inhibited by recombinant NPY protein in vitro. This inhibitory effect could be blocked by selected NPY1R antagonist BIBP3226. Furthermore, overexpression of NPY1R could significantly inhibit HCC cell proliferation. Knockdown of NPY1R promoted cell multiplication in vitro and increased tumorigenicity and tumor growth in vivo. NPY1R was found to participate in the inhibition of cell proliferation via inactivating mitogen-activated protein kinase signal pathway in HCC cells. Collectively, NPY1R plays an inhibitory role in tumor growth and may be a promising therapeutic target for HCC.
Basic Medical Research Centre in Medical College of Nantong University, Nantong, China.
Xiufang
X
Lv
Basic Medical Research Centre in Medical College of Nantong University, Nantong, China.
Fengbo
F
Zhao
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/2200, Xietu Road, Shanghai, 200032, China.
Xisong
X
Huo
Department of General Surgery, The Affiliated Hospital, Nantong University, Nantong, China.
Weidong
W
Tang
Basic Medical Research Centre in Medical College of Nantong University, Nantong, China.
Baoying
B
Hu
Basic Medical Research Centre in Medical College of Nantong University, Nantong, China.
Xiu
X
Gong
Basic Medical Research Centre in Medical College of Nantong University, Nantong, China.
Juan
J
Yang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/2200, Xietu Road, Shanghai, 200032, China.
Qiujin
Q
Shen
Basic Medical Research Centre in Medical College of Nantong University, Nantong, China. wxqin@sjtu.edu.cn.|State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/2200, Xietu Road, Shanghai, 200032, China. wxqin@sjtu.edu.cn.
Wenxin
W
Qin
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D017476:Receptors, Neuropeptide Y / Q000096:biosynthesis*
D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor
HCC; NPY; NPY1R; Proliferation