title: Overexpression of Inhibitor of Growth 4 Enhances Radiosensitivity in Non-Small Cell Lung Cancer Cell Line SPC-A1.
abstract: Inhibitor of growth 4 is a member of the inhibitor of growth family proteins, which is involved in cell apoptosis, migration, invasion, and cell cycle progress. In this study, we investigated the inhibitor of growth 4 level in non-small cell lung cancer tissues and explored the antitumor activity of inhibitor of growth 4 in vitro and in vivo using non-small cell lung cancer cell line SPC-A1 and its underlying molecular mechanisms. We also explored its role on the radiosensitivity in SPC-A1 cells. The level of inhibitor of growth 4 protein was significantly decreased in 28 cases of non-small cell lung cancer tissues in comparison with corresponding noncancerous lung epithelial tissues. Upregulation of inhibitor of growth 4 by plasmid pcDNA3.1-ING4 delivery could suppress proliferation and increase apoptosis of SPC-A1 cells both in vitro and in vivo. Additionally, we found that overexpression of inhibitor of growth 4 in SPC-A1 cell line could lead to a higher Bcl-2/Bax ratio, which might be an important factor in the apoptosis regulation. Furthermore, overexpression of inhibitor of growth 4 enhanced the radiosensitivity of SPC-A1 cells to irradiation. Inhibitor of growth 4 upregulation plus radiotherapy induced synergistic tumor suppression in SPC-A1 xenografts implanted in athymic nude mice. Thus, the restoration of inhibitor of growth 4 function might provide a potential strategy for non-small cell lung cancer radiosensitization.
authors.affiliation: 1 Department of Medical Oncology, Nanjing Medical University Affiliated Cancer Hospital of Jiangsu Province, Cancer Institution of Jiangsu Province, Nanjing, China.|2 Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Pan
authors.affiliation: 3 Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: 2 Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Bian
authors.affiliation: 4 Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: 5 Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 2 Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Wei
authors.affiliation: 2 Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000532:radiotherapy; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D051379:Mice; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D025521:Tumor Suppressor Proteins
keywords: ING4; NSCLC; apoptosis; gene therapy; radiosensitivity