Gemcitabine inhibits viability, growth, and metastasis of osteosarcoma cell lines

被引:29
作者
Ando, T
Ichikawa, J
Okamoto, A
Tasaka, K
Nakao, A
Hamada, Y
机构
[1] Yamanashi Univ, Dept Orthopaed Surg, Fac Med, Tamaho, Yamanashi 4093898, Japan
[2] Univ Yamanashi, Dept Immunol, Fac Med, Yamanashi 4093898, Japan
[3] Juntendo Univ, Atopy Res Ctr, Sch Med, Tokyo 1138421, Japan
关键词
gemcitabine; osteosarcoma; apoptosis; metastasis;
D O I
10.1016/j.orthres.2005.01.010
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Gemcitabine (dFdCyd) is an analog of cytosine arabinoside with anti-tumor activity in several human cancers. However, the efficacy of this compound in osteosarcoma has not been fully elucidated. Here we assessed the anti-tumor activity of gemcitabine using osteosarcome cell lines. In 9 human osteosarcoma cell lines (G292, HOS, MG63, NY, SaOS, HuO, HuO-3N1, HuO9, HuO9-N2), gemcitabine at the doses of > 100 nM showed significant cytotoxicity. In HOS and MG63 cell lines, gemcitabine inhibited DNA synthesis as determined by IdU labeling assay and induced apoptosis as determined by DNA fragmentation assay and May-Giemsa staining. In C3H mice inoculated s.c. with a murine osteosarcoma cell line, LM8, treatment of the mice with gemcitabine showed reduced size of the primary tumor associated with increased apoptotic cells and a virtual absence of metastatic lesions in the lung. Gemcitabine thus had anti-tumor activity on osteosarcoma cell lines both in vitro and in vivo. The result would provide a cellular basis for application of gemcitabine to patients with osteosarcoma. (c) 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:964 / 969
页数:6
相关论文
共 17 条
[1]  
Asai T, 1998, INT J CANCER, V76, P418, DOI 10.1002/(SICI)1097-0215(19980504)76:3<418::AID-IJC21>3.3.CO
[2]  
2-E
[3]   High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: Preliminary results of an Italian sarcoma group/Scandinavian sarcoma group pilot study [J].
Bacci, G ;
Ferrari, S ;
Longhi, A ;
Picci, P ;
Mercuri, M ;
Alvegard, TA ;
Saeter, G ;
Donati, D ;
Manfrini, M ;
Lari, S ;
Briccoli, A ;
Forni, C .
JOURNAL OF CHEMOTHERAPY, 2002, 14 (02) :198-206
[4]   Gemcitabine-induced programmed cell death (apoptosis) of human pancreatic carcinoma is determined by Bcl-2 content [J].
Bold, RJ ;
Chandra, J ;
McConkey, DJ .
ANNALS OF SURGICAL ONCOLOGY, 1999, 6 (03) :279-285
[5]   THE INFLUENCE OF THE SCHEDULE AND THE DOSE OF GEMCITABINE ON THE ANTITUMOR EFFICACY IN EXPERIMENTAL HUMAN CANCER [J].
BOVEN, E ;
SCHIPPER, H ;
ERKELENS, CAM ;
HATTY, SA ;
PINEDO, HM .
BRITISH JOURNAL OF CANCER, 1993, 68 (01) :52-56
[6]  
BRAAKHUIS BJM, 1991, CANCER RES, V51, P211
[7]  
BRAAKHUIS BJM, 1995, SEMIN ONCOL, V22, P42
[8]   Phase I clinical trial of fixed-dose rate infusional gemcitabine and dacarbazine in the treatment of advanced soft tissue sarcoma, with assessment of gemcitabine triphosphate accumulation [J].
Buesa, JM ;
Losa, R ;
Fernández, A ;
Sierra, M ;
Esteban, E ;
Díaz, A ;
López-Pousa, A ;
Fra, J .
CANCER, 2004, 101 (10) :2261-2269
[9]   PHASE-II TRIAL OF GEMCITABINE (2,2'-DIFLUORODEOXYCYTIDINE) IN PATIENTS WITH ADENOCARCINOMA OF THE PANCREAS [J].
CASPER, ES ;
GREEN, MR ;
KELSEN, DP ;
HEELAN, RT ;
BROWN, TD ;
FLOMBAUM, CD ;
TROCHANOWSKI, B ;
TARASSOFF, PG .
INVESTIGATIONAL NEW DRUGS, 1994, 12 (01) :29-34
[10]  
EIBER F, 1987, J CLIN ONCOL, V5, P21