rAd-p53 enhances the sensitivity of human gastric cancer cells to chemotherapy

被引:21
作者
Chen, Guang-Xia [1 ]
Zheng, Li-Hong [2 ]
Liu, Shi-Yu [1 ]
He, Xiao-Hua [1 ]
机构
[1] First Peoples Hosp Xuzhou, Dept Gastroenterol, Xuzhou 221002, Jiangsu Provinc, Peoples R China
[2] Yantai Econ & Technol Dev Zone Hosp, Yantai 264006, Shandong, Peoples R China
关键词
Gastric cancer; rAd-p53; Oxaliplatin; Chemosensitivity; Apoptosis; P53 MUTATION LOAD; HEPATOCELLULAR-CARCINOMA; LUNG-CANCER; INDUCED APOPTOSIS; GENE; DISEASE; SURVIVAL; HOTSPOT; TUMORS; LIVER;
D O I
10.3748/wjg.v17.i38.4289
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy. METHODS: Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin (OXA) alone, or a combination of both. Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry. RESULTS: Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time-and dose-dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells. Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompanied by increased expression of caspase-3. CONCLUSION: rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis. Thus, our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment. (C) 2011 Baishideng. All rights reserved.
引用
收藏
页码:4289 / 4297
页数:9
相关论文
共 30 条
  • [1] p53 Mutations and survival in stage I non-small-cell lung cancer: Results of a prospective study
    Ahrendt, SA
    Hu, YC
    Buta, M
    McDermott, MP
    Benoit, N
    Yang, SC
    Wu, L
    Sidransky, D
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (13) : 961 - 970
  • [2] SELECTIVE G-MUTATION TO T-MUTATION OF P53 GENE IN HEPATOCELLULAR-CARCINOMA FROM SOUTHERN AFRICA
    BRESSAC, B
    KEW, M
    WANDS, J
    OZTURK, M
    [J]. NATURE, 1991, 350 (6317) : 429 - 431
  • [3] The Bcl-2 family: roles in cell survival and oncogenesis
    Cory, S
    Huang, DCS
    Adams, JM
    [J]. ONCOGENE, 2003, 22 (53) : 8590 - 8607
  • [4] DEJONG D, 1994, CANCER RES, V54, P256
  • [5] TP53 DNA contact mutations are selectively associated with allelic loss and have a strong clinical impact in head and neck cancer
    Erber, R
    Conradt, C
    Homann, N
    Enders, C
    Finckh, M
    Dietz, A
    Weidauer, H
    Bosch, FX
    [J]. ONCOGENE, 1998, 16 (13) : 1671 - 1679
  • [6] Fan R, 2000, CANCER EPIDEM BIOMAR, V9, P1037
  • [7] Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation
    Figueiredo, BC
    Sandrini, R
    Zambetti, GP
    Pereira, RM
    Cheng, C
    Liu, W
    Lacerda, L
    Pianovski, MA
    Michalkiewicz, E
    Jenkins, J
    Rodriguez-Galindo, C
    Mastellaro, MJ
    Vianna, S
    Watanabe, F
    Sandrini, F
    Arram, SBI
    Boffetta, P
    Ribeiro, RC
    [J]. JOURNAL OF MEDICAL GENETICS, 2006, 43 (01) : 91 - 96
  • [8] Rapid and sensitive p53 alteration analysis in biopsies from lung cancer patients using a functional assay and a universal oligonucleotide array: A prospective study
    Fouquet, C
    Antoine, M
    Tisserand, P
    Favis, R
    Wislez, M
    Commo, F
    Rabbe, N
    Carette, MF
    Milleron, B
    Barany, F
    Cadranel, J
    Zalcman, G
    Soussi, T
    [J]. CLINICAL CANCER RESEARCH, 2004, 10 (10) : 3479 - 3489
  • [9] Beyond Li Fraumeni Syndrome: Clinical Characteristics of Families With p53 Germline Mutations
    Gonzalez, Kelly D.
    Noltner, Katie A.
    Buzin, Carolyn H.
    Gu, Dongqing
    Wen-Fong, Cindy Y.
    Nguyen, Vu Q.
    Han, Jennifer H.
    Lowstuter, Katrina
    Longmate, Jeffrey
    Sommer, Steve S.
    Weitzel, Jeffrey N.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (08) : 1250 - 1256
  • [10] Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease
    Goodman, JE
    Hofseth, LJ
    Hussain, SP
    Harris, CC
    [J]. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2004, 44 (01) : 3 - 9