Synergistic antitumor efficacy by combining adriamycin with recombinant human endostatin in an osteosarcoma model

被引:27
作者
Xu, Hairong [1 ]
Niu, Xiaohui [1 ]
Zhang, Qing [1 ]
Hao, Lin [1 ]
Ding, Yi [1 ]
Liu, Weifeng [1 ]
Yao, Lu [2 ]
机构
[1] Peking Univ, Beijing Ji Shui Tan Hosp, Dept Orthoped Oncol Surg, Beijing 100035, Peoples R China
[2] Peking Univ, Sch Basic Med Sci, Dept Pathol, Beijing 100035, Peoples R China
关键词
osteosarcoma; antiangiogenic therapy; combination therapy; synergistic effect; POSTOPERATIVE PROGRESSION; ADJUVANT CHEMOTHERAPY; PULMONARY METASTASIS; TUMOR ANGIOGENESIS; OSTEOGENIC-SARCOMA; THERAPY; CANCER; GROWTH; ANGIOSTATIN; MICE;
D O I
10.3892/ol.2011.334
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In the last 15 years, chemotherapy-based therapeutic regimens for the treatment of osteosarcoma have failed to demonstrate improved survival rates. Novel approaches, including targeted therapy and antiangiogenic therapy, may provide new methods for the treatment of osteosarcoma, one of the most deadly malignant diseases. In the present study, the therapeutic efficacy of an endogenous angiogenesis inhibitor, endostatin, was tested in combination with the chemotherapeutic agent, adriamycin. BALB/c mice, aged 4-6 weeks were fed animal chow and had access to water ad libitum. The mice were divided into groups and injected with tumor cells. Immunohistochemical staining was performed to identify the microvessel density. The TUNEL technique was also used to determine the apoptotic index. The combination of endostatin and adriamycin produced marked synergistic antitumor activity in a mouse osteosarcoma model. These findings provide new guidelines for designing future clinical trials and for the application of currently available clinical drugs (endostatin has been approved for clinical use) in the treatment of osteosarcoma.
引用
收藏
页码:773 / 778
页数:6
相关论文
共 37 条
[1]  
Alvarez AA, 1999, CLIN CANCER RES, V5, P587
[2]   Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy [J].
Bacci, G ;
Longhi, A ;
Fagioli, F ;
Briccoli, A ;
Versari, M ;
Picci, P .
EUROPEAN JOURNAL OF CANCER, 2005, 41 (18) :2836-2845
[3]   Targeting angiogenesis for the treatment of sarcoma [J].
Balasubramanian, Lakshmi ;
Evens, Andrew M. .
CURRENT OPINION IN ONCOLOGY, 2006, 18 (04) :354-359
[4]   Bone Tumors in Adolescents and Young Adults [J].
Bielack, Stefan S. ;
Carrle, Dorothe ;
Hardes, Jendrik ;
Schuck, Andreas ;
Paulussen, Michael .
CURRENT TREATMENT OPTIONS IN ONCOLOGY, 2008, 9 (01) :67-80
[5]   Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126 [J].
Bozec, A. ;
Lassalle, S. ;
Gugenheim, J. ;
Fischel, J-L ;
Formento, P. ;
Hofman, P. ;
Milano, G. .
BRITISH JOURNAL OF CANCER, 2006, 95 (06) :722-728
[6]   Angiogenesis in cancer and other diseases [J].
Carmeliet, P ;
Jain, RK .
NATURE, 2000, 407 (6801) :249-257
[7]   Current strategies of chemotherapy in osteosarcoma [J].
Carrle, Dorothe ;
Bielack, Stefan S. .
INTERNATIONAL ORTHOPAEDICS, 2006, 30 (06) :445-451
[8]   Therapy for osteosarcoma: Where do we go from here? [J].
Chou A.J. ;
Geller D.S. ;
Gorlick R. .
Pediatric Drugs, 2008, 10 (5) :315-327
[9]   Metastatic osteosarcoma - Results of two consecutive therapeutic trials at St. Jude Children's Research Hospital [J].
Daw, NC ;
Billups, CA ;
Rodriguez-Galindo, C ;
McCarville, MB ;
Rao, BN ;
Cain, AM ;
Jenkins, JJ ;
Neel, MD ;
Meyer, WH .
CANCER, 2006, 106 (02) :403-412
[10]   Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: Study in a human-like rat orthotopic tumor [J].
Dutour, A ;
Monteil, J ;
Paraf, F ;
Charissoux, JL ;
Kaletta, C ;
Sauer, B ;
Naujoks, K ;
Rigaud, M .
MOLECULAR THERAPY, 2005, 11 (02) :311-319