Cooperative inhibition of renal cancer growth by anti-epidermal growth factor receptor antibody and protein kinase A antisense oligonucleotide

被引:69
作者
Ciardiello, F
Caputo, R
Bianco, R
Damiano, V
Pomatico, G
Pepe, S
Bianco, AR
Agrawal, S
Mendelsohn, J
Tortora, G
机构
[1] Univ Naples Federico II, Fac Med & Chirurg, Cattedra Oncol Med, Dipartimento Endocrinol & Oncol Mol & Clin, I-80131 Naples, Italy
[2] Hybridon Inc, Cambridge, MA USA
[3] Univ Texas, Md Anderson Canc Ctr, Houston, TX USA
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 1998年 / 90卷 / 14期
关键词
D O I
10.1093/jnci/90.14.1087
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: The expression of epidermal growth factor receptor (EGFR) and type I cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKAI) is associated with neoplastic transformation. By use of human renal cancer cell lines (i,e,, 769-P, ACHN, A498, and SW839), we investigated the antiproliferative activity and the antitumor activity of an anti-EGFR humanized chimeric mouse monoclonal antibody, MAb C225, and a novel mixed backbone 18-mer antisense oligonucleotide, HYB 190, that targets expression of the RI alpha regulatory subunit of PKAI, Methods: The antiproliferative activity of MAb C225 and oligonucleotide HYB 190, alone or in combination, on different renal cancer cell lines was determined by monitoring cell growth in soft agar, In addition, the induction of apoptosis by treatment with the anti-EGFR antibody and/or antisense PKAI oligonucleotides was evaluated by flow cytometric analysis of fragmented DNA, The antitumor activity of MAb C225 and oligonucleotide HYB 190 was determined in athymic mice bearing established ACHN tumor xenografts, Cell proliferation and tumor growth data were evaluated for statistical significance using Student's t test; reported P values are two-sided. Results: MAb C225 and oligonucleotide HYB 190 inhibited colony formation in soft agar in a dose-dependent manner for all renal cancer cell lines tested, We observed a potentiation of growth inhibition and induction of apoptosis when 769-P cells and ACHN cells were treated with both agents. Combination treatment with MAb C225 and oligonucleotide HYB 190 caused regression of ACHN tumor xenografts, whereas single-agent treatment only delayed tumor growth. Conclusion: The combination of anti-EGFR MAb C225 and HYB 190 antisense PKAI oligonucleotides HYB 190 exhibited cooperative antiproliferative effects and cooperative antitumor effects on EGFR and PKAI-expressing human renal cancer cell Lines.
引用
收藏
页码:1087 / 1094
页数:8
相关论文
共 53 条
  • [1] EFFICACY OF ANTIBODIES TO EPIDERMAL GROWTH-FACTOR RECEPTOR AGAINST KB CARCINOMA INVITRO AND IN NUDE-MICE
    ABOUDPIRAK, E
    HURWITZ, E
    PIRAK, ME
    BELLOT, F
    SCHLESSINGER, J
    SELA, M
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1988, 80 (20) : 1605 - 1611
  • [2] Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies
    Agrawal, S
    Jiang, ZW
    Zhao, QY
    Shaw, D
    Cai, QY
    Roskey, A
    Channavajjala, L
    Saxinger, C
    Zhang, RW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (06) : 2620 - 2625
  • [3] Antisense oligonucleotides: Towards clinical trials
    Agrawal, S
    [J]. TRENDS IN BIOTECHNOLOGY, 1996, 14 (10) : 376 - 387
  • [4] ALLY S, 1989, CANCER RES, V49, P5650
  • [5] ARTEAGA CL, 1994, CANCER RES, V54, P4703
  • [6] ATLAS I, 1992, CANCER RES, V52, P3335
  • [7] ANTITUMOR EFFECTS OF DOXORUBICIN IN COMBINATION WITH ANTIEPIDERMAL GROWTH-FACTOR RECEPTOR MONOCLONAL-ANTIBODIES
    BASELGA, J
    NORTON, L
    MASUI, H
    PANDIELLA, A
    COPLAN, K
    MILLER, WH
    MENDELSOHN, J
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (16) : 1327 - 1333
  • [8] Type I Receptor Tyrosine Kinases as Targets for Therapy in Breast Cancer
    Baselga, Jose
    Mendelsohn, John
    [J]. JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 1997, 2 (02) : 165 - 174
  • [9] BOS M, 1996, P AN M AM SOC CLIN, V15, pA1381
  • [10] Buchdunger E, 1995, CLIN CANCER RES, V1, P813