Browse > Article

The Combined Effect of Gamma Knife Irradiation and p53 Gene Transfection in Human Malignant Glioma Cell Lines  

Kim, Jeong-Eun (Departments of Neurosurgery, Seoul National University College of Medicine)
Paek, Sun-Ha (Departments of Neurosurgery, Seoul National University College of Medicine)
Kim, Dong-Gyu (Departments of Neurosurgery, Seoul National University College of Medicine)
Chung, Hyun-Tai (Departments of Neurosurgery, Seoul National University College of Medicine)
Kim, Young-Yim (Departments of Clinical Research Institute, Seoul National University College of Medicine)
Jung, Hee-Won (Departments of Neurosurgery, Seoul National University College of Medicine)
Publication Information
Journal of Korean Neurosurgical Society / v.37, no.1, 2005 , pp. 48-53 More about this Journal
Abstract
Objective: The purpose of this study is to elucidate in vitro responses to combined gamma knife irradiation and p53 gene transfection on human malignant glioma cell lines. Methods: Two malignant human glioma cell lines, U87MG (p53-wild type) and U373MG (p53-mutant) were transfected with an adenoviral vector containing p53 (MOI of 50) before and after applying 20Gy of gamma irradiation. Various assessments were performed, including, cell viability by MTT assay; apoptosis by annexin assay; and cell cycle by flow cytometry, for the seven groups: mock, p53 only, gamma knife (GK) only, GK after LacZ, LacZ after GK, GK after p53, p53 after GK. Results: Cell survival decreased especially, in the subgroup transfected with p53 after gamma irradiation. Apoptosis tended to increase in p53 transfected U373 MG after gamma irradiation (apoptotic rate, 38.9%). The G2-M phase cell cycle arrest markedly increased by transfecting with p53, 48 hours after gamma knife irradiation in U373 MG (G2-M phase, 90.8%). Conclusion: These results suggest that the in vitro effects of combined gamma knife irradiation and p53 gene transfection is an augmentation of apoptosis and G2-M phase cell cycle arrest, which are more exaggerated in U373 MG with p53 transfection after gamma knife irradiation.
Keywords
Adenovirus; Gamma knife; Gene therapy; Malignant glioma; p53; Radiation;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Chung HT, Kim JE, Kim DG, Jung HW : A stereotactic device for gamma knife irradiation to cell lines. J Korean Neurosurg Soc 35 : 639-642, 2004
2 El-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, et al : WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54 : 1169-1174, 1994
3 Kim SK, Wang KC, Cho BK, Chung HT, Kim YY, Lim SY, et al : Interaction between p53 and p16 expressed by adenoviral vectors in human malignant glioma cell lines. J Neurosurg 97 : 143-150, 2002   DOI   ScienceOn
4 Lowe SW, Ruley HE, Jacks T, Housman DE : p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74 : 957-967, 1993   DOI   ScienceOn
5 Mcllwrath AJ, Vasey PA, Ross GM, Brown R : Cell cycle arrests and radiosensitivity of human tumor cell lines: dependence on wild-type p53 for radiosensitivity. Cancer Res 54 : 3718-3722, 1994
6 Raycroft L, Wu HY, Lozano G : Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science 249 : 1049-1051, 1990   DOI   PUBMED
7 Wara WM, Bauman GS, Sneed PK : Brain, brain stem and cerebellum, in Perez CA, Brady LW (eds) : Principles and Practice of Radiation Oncology. Philadelphia : Lippincott-Raven, 1998, pp777-828
8 El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, et al : WAF1, a potential mediator of p53 tumor suppression. Cell 75 : 817-825, 1993   DOI   ScienceOn
9 Black PM : Brain tumor. part 2. N Engl J Med 324 : 1555-1564, 1991   DOI   PUBMED   ScienceOn
10 Gomez-Manzano C, Fueyo J, Kyritsis AP, Steck PA, Roth JA, McDonnell TJ, et al : Adenovirus-mediated transfer of the p53 gene products rapid and generalized death of human glioma cells via apoptosis. Cancer Res 56 : 694-699, 1996
11 Kim JE, Paek SH, Chung HT, Kim DG, Jung HW : in vitro biological response of malignant glioma cell lines to gamma knife irradiation. J Korean Neurosurg Soc 35 : 599-604, 2004
12 Putzer BM, Bramson JL, Addison CL, Hitt M, Siegel PM, Muller WJ, et al : Combination therapy with interleukin-2 and wild-type p53 expressed by adenoviral vectors potentiates tumor regression in a murine model of breast cancer. Hum Gene Ther 9 : 707-718, 1998   DOI   ScienceOn
13 Owen-Schaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T, et al : Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol Cell Biol 15 : 3032-3040, 1995   DOI
14 Salcman M : Surgical resection of malignant brain tumors : who benefits? Oncology 32 : 931-941, 1988
15 Badie B, Goh CS, Klaver J, Herweijer H, Boothman DA : Combined radiation and p53 gene therapy of malignant glioma cells. Cancer Gene Ther 6 : 155-162, 1999   DOI   ScienceOn
16 Haupt Y, Rowan S, Oren M : p53-mediated apoptosis in HeLa cells can be overcome by excess pRB. Oncogene 10 : 1563-1571, 1997
17 Levine AJ, Momand J, Finlay CA : The p53 tumour suppressor gene. Nature 351 : 453-456, 1991   DOI   ScienceOn
18 Slichenmyer WJ, Nelson WG, Slebos RJ, Kastan MB : Loss of a p53- associated G1 checkpoint does not decrease cell survival following DNA damage. Cancer Res 53 : 4164-4168, 1993
19 Clayman GL, el-Naggar AK, Roth JA, Zhang WW, Goepfert H, Tayler DL, et al : In vivo molecular therapy with p53 adenovirus for microscopic residual head and neck squamous carcinoma. Cancer Res 55 : 1-6, 1995
20 Frankel RH, Bayona W, Koslow M, Newcomb EW : p53 mutations in human malignant gliomas : comparison of loss of heterozygosity with mutation frequency. Cancer Res 52 : 1427-1433, 1992
21 Polednak AP, Flannery JT : Brain, other central nervous system, and eye cancer. Cancer 75(Suppl 1) : 330-337, 1995   DOI   PUBMED   ScienceOn
22 Li H, Lochmuller H, Yong VW, Karpati G, Nalbantoglu J : Adenovirusmediated wild-type p53 gene transfer and overexpression induces apoptosis of human glioma cells independent of endogenous p53 status. J Neuropathol Exp Neurol 56 : 872-878, 1997   DOI   ScienceOn
23 Gotz C, Montenrh M : p53 : DNA damage, DNA repair, and apoptosis. Rev Physiol Biochem Pharmacol 127 : 65-95, 1995   DOI
24 Miyashita T, Reed JC : Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80 : 293-299, 1995   DOI   PUBMED   ScienceOn
25 von Deimling A, Eibl RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, et al : p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 52 : 2987-2990, 1992
26 Kock H, Harris MP, Anderson SC, Machemer T, Hancock W, Sutjipto S, et al : Adenovirus-mediated p53 gene transfer suppresses growth of human glioblastoma cells in vitro and in vivo. Int J Cancer 67 : 805- 815, 1996   DOI   ScienceOn
27 Smith ML, Chen IT, Zhan Q, O'Connor PM, Fornace AJ Jr : Involvement of the p53 tumor suppressor in repair of UV-type DNA damage. Oncogene 10 : 1053-1059, 1995