Inhibitory effect of radiotherapy combined with weekly recombinant human endostatin on the human pulmonary adenocarcinoma A549 xenografts in nude mice

被引:24
作者
Jiang, Xiao-dong [2 ,3 ]
Dai, Peng [3 ]
Wu, Jin [3 ]
Song, Da-an [3 ]
Yu, Jin-ming [1 ]
机构
[1] Shandong Canc Hosp, Dept Radiat Oncol, Jinan 250117, Shandong, Peoples R China
[2] Tianjin Med Univ, Grad Sch, Tianjin 300021, Peoples R China
[3] Lianyungang First Peoples Hosp, Dept Oncol, Lianyungang 222002, Peoples R China
关键词
Radiotherapy; Recombinant human endostatin; Pulmonary adenocarcinoma A549 cells; TUMOR VASCULATURE; ANTIANGIOGENIC ACTIVITY; RADIATION; THERAPY; NORMALIZATION; GROWTH; CANCER; RADIORESPONSE; ANGIOGENESIS; CARCINOMA;
D O I
10.1016/j.lungcan.2010.09.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of this study was to investigate the inhibitory effect of radiotherapy combined with weekly recombinant human endostatin (RHES) on the human pulmonary adenocarcinoma A549 xenografts in nude mice. The 40 A549 xenograft nude mice models were randomly divided into 4 groups (each group with 10 nude mice). Single radiotherapy group (group 1) was given a single external irradiation (6MV-X ray, 10 Gy) and peritumoral subcutaneous injection of 0.2 ml normal saline every day for 7 days. Single RUES group (group 2) was given peritumoral subcutaneous injection of 0.2 ml RHES (0.75 mg/ml) for 7 days. Combination therapy group (group 3) was given radiotherapy as the same as group 1 and RHES as the same as group 2. Control group was given normal saline as the same as group 1. The tumor volume was smaller in group 3 than in control group from the 8th day after treatment (P < 0.05) and tumor regression occurred from the second week after treatment in group 3. On the 15th day after treatment, the inhibitory rates of tumor volume were 69.65%, 92.64% and 116.4% in groups 2, 1 and 3, respectively; MVD number was lower in group 3 than in group I (P < 0.05); there was no statistical significance in VEGF expression between group 2 and control group as well as between group 3 and group 1 (P > 0.05). Apoptosis was marked in group 3. Radiotherapy combined with weekly RHES can significantly inhibit tumor growth and earlier induce tumor regression, which may be related to the improvement of tumor hypoxia and the inhibition of radiation-induced tumor angiogenesis. Short-term application (1 week) of RUES is beneficial to clinical practice. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:165 / 171
页数:7
相关论文
共 19 条
[1]   Endostatin's antiangiogenic signaling network [J].
Abdollahi, A ;
Hahnfeldt, P ;
Maercker, C ;
Gröne, HJ ;
Debus, J ;
Ansorge, W ;
Folkman, J ;
Hlatky, L ;
Huber, PE .
MOLECULAR CELL, 2004, 13 (05) :649-663
[2]   AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients [J].
Batchelor, Tracy T. ;
Sorensen, A. Gregory ;
di Tomaso, Emmanuelle ;
Zhang, Wei-Ting ;
Duda, Dan G. ;
Cohen, Kenneth S. ;
Kozak, Kevin R. ;
Cahill, Daniel P. ;
Chen, Poe-Jou ;
Zhu, Mingwang ;
Ancukiewicz, Marek ;
Mrugala, Maciej M. ;
Plotkin, Scott ;
Drappatz, Jan ;
Louis, David N. ;
Ivy, Percy ;
Scadden, David T. ;
Benner, Thomas ;
Loeffler, Jay S. ;
Wen, Patrick Y. ;
Jain, Rakesh K. .
CANCER CELL, 2007, 11 (01) :83-95
[3]   Endostatin gene transfer in murine lung carcinoma cells induces vascular endothelial growth factor secretion resulting in up-regulation of in vivo tumorigenecity [J].
Cui, R ;
Takahashi, K ;
Takahashi, F ;
Tanabe, KK ;
Fukuchi, Y .
CANCER LETTERS, 2006, 232 (02) :262-271
[4]   Endostatin exhibits a direct antitumor effect in addition to its antiangiogenic activity in colon cancer cells [J].
Dkhissi, F ;
Lu, H ;
Soria, C ;
Opolon, P ;
Griscelli, F ;
Liu, HF ;
Khattar, P ;
Mishal, Z ;
Perricaudet, M ;
Li, H .
HUMAN GENE THERAPY, 2003, 14 (10) :997-1008
[5]   Antiangiogenesis in cancer therapy - endostatin and its mechanisms of action [J].
Folkman, J .
EXPERIMENTAL CELL RESEARCH, 2006, 312 (05) :594-607
[6]   Tumor angiogenesis and tissue factor [J].
Folkman, J .
NATURE MEDICINE, 1996, 2 (02) :167-168
[7]  
Gorski DH, 1999, CANCER RES, V59, P3374
[8]   Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin [J].
Herbst, RS ;
Mullani, NA ;
Davis, DW ;
Hess, KR ;
McConkey, DJ ;
Charnsangavej, C ;
O'Reilly, MS ;
Kim, HW ;
Baker, C ;
Roach, J ;
Ellis, LM ;
Rashid, A ;
Pluda, J ;
Bucana, C ;
Madden, TL ;
Tran, HT ;
Abbruzzese, JL .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (18) :3804-3814
[9]   Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice [J].
Itasaka, Satoshi ;
Komaki, Ritsuko ;
Herbst, Roy S. ;
Shibuya, Keiko ;
Shintani, Tomoaki ;
Hunter, Nancy R. ;
Onn, Amir ;
Bucana, Corazon D. ;
Milas, Luka ;
Ang, K. Kjan ;
O'Reilly, Michael S. .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2007, 67 (03) :870-878
[10]   Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy [J].
Jain, RK .
NATURE MEDICINE, 2001, 7 (09) :987-989