Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer.
Celecoxib inhibits growth of tumors in a syngeneic rat liver metastases model for colorectal cancer.
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DOI：
10.1007/s00280-007-0668-4
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发表时间：
2008-10
影响因子：
3
通讯作者：
Kuppen, Peter J. K.
中科院分区：
文献类型：
--
作者：
de Heer, Pieter;Sandel, Maro H.;Guertens, Gunther;de Boeck, Gert;Koudijs, Margaretha M.;Nagelkerke, J. Fred;Junggeburt, Jan M. C.;de Bruijn, Ernst A.;van de Velde, Cornelis J. H.;Kuppen, Peter J. K.
关键词：
非甾体抗炎药（NSAID）已被证明可以降低环氧化酶-2（考克斯-2）过表达的结直肠癌患者的结直肠癌风险。本研究旨在评价考克斯-2抑制剂塞来昔布对同系大鼠模型CC 531结肠直肠癌肝转移生长的抑制作用。通过用塞来昔布处理CC 531肿瘤细胞培养物来评价塞来昔布对体外细胞活力的影响。在体内，Wag/Rij大鼠在肝脏的两个部位接种CC 531肿瘤细胞，并在肿瘤接种前一周或肿瘤接种后立即开始接受塞来昔布治疗。对照组大鼠接种，不进行处理。肿瘤接种后三周处死大鼠。测定肿瘤大小、免疫细胞浸润、caspase-3活性、PGE 2和塞来昔布水平。CC 531肿瘤无考克斯-2表达。塞来昔布治疗以剂量依赖性方式显著抑制肿瘤生长。塞来昔布治疗后免疫细胞浸润减少，表明免疫系统不参与阻止肿瘤生长。如果在肿瘤接种前开始治疗，则肿瘤胱天蛋白酶-3水平仅显著增加。塞来昔布血清浓度从0.84 μg/ml开始显著抑制CC 531肝肿瘤的生长。相反，塞来昔布的体外浓度至少需要12 μg/ml才能影响肿瘤细胞的活力。这些结果表明，塞来昔布对肿瘤生长的抑制作用不是通过直接的细胞毒性，而是通过创造一个不利于肿瘤生长的环境。
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531. The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE2 and celecoxib levels were determined. CC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 μg/ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 μg/ml were needed to affect tumor cell viability. These results suggest that the inhibitory effects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.
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影响因子：
24.5
作者：
Buskens, CJ;Sivula, A;Ristimäki, A
通讯作者：
Ristimäki, A
影响因子：
6.4
作者：
Germann, A;Dihlmann, S;Koesters, R
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Koesters, R
影响因子：
5
作者：
Jonges, LE;Nagelkerke, JF;Kuppen, PJK
通讯作者：
Kuppen, PJK
影响因子：
3.7
作者：
Kojima, M;Morisaki, T;Tanaka, M
通讯作者：
Tanaka, M
影响因子：
8.8
作者：
MARINELLI, A;DIJKSTRA, FR;VANDEVELDE, CJH
通讯作者：
VANDEVELDE, CJH