Regression of prostate tumors upon combination of hormone ablation therapy and celecoxib in vivo.
Regression of prostate tumors upon combination of hormone ablation therapy and celecoxib in vivo.
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DOI：
10.1002/pros.21297
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发表时间：
2011-06-01
期刊：
影响因子：
2.8
通讯作者：
Borgstroem, Per
中科院分区：
文献类型：
--
作者：
Abedinpour, Parisa;Baron, Veronique T.;Welsh, John;Borgstroem, Per
激素消融是晚期雄激素依赖性前列腺癌的标准治疗方法。虽然肿瘤通常在一开始就消退，但癌症不可避免地向雄激素非依赖性发展，部分原因是耐药机制的发展，部分原因是在组织水平上雄激素的戒断没有完全实现。目前的研究工作集中在新的治疗策略，将增加雄激素的有效性和延迟复发。我们使用一种同基因的伪正交异性前列腺癌小鼠模型来测试雄激素戒断联合fda批准的COX-2抑制剂塞来昔布的疗效。将gfp标记的trump - c2细胞与前列腺组织共同植入背室模型，使肿瘤建立并血管化。采用荧光活体显微镜（IVM）实时监测肿瘤生长和血管生成情况。通过手术阉割或化学激素消融术，单独或联合塞来昔布（15mg /kg，每日两次），实现小鼠雄激素戒断。塞来昔布单用主要通过诱导有丝分裂失败导致细胞凋亡增加来抑制前列腺肿瘤的生长。令人惊讶的是，塞来昔布没有明显的血管抑制活性。手术或化学阉割阻止了前列腺肿瘤的生长，另一方面，这与肿瘤血管系统的破坏有关。最后，雄激素停用联合塞来昔布通过减少血管生成、增加有丝分裂停止和细胞凋亡导致肿瘤消退。塞来昔布是一种相对安全的cox -2选择性抗炎药，可显著提高体内雄激素停药的疗效，值得进一步研究作为晚期前列腺癌的补充治疗。
Hormonal ablation is the standard of treatment for advanced androgen-dependent prostate cancer. Although tumor regression is usually achieved at first, the cancer inevitably evolves toward androgen-independence, in part because of the development of mechanisms of resistance and in part because at the tissue level androgen withdrawal is not fully attained. Current research efforts are focused on new therapeutic strategies that will increase the effectiveness of androgen withdrawal and delay recurrence. We used a syngeneic pseudo-orthotropic mouse model of prostate cancer to test the efficacy of combining androgen withdrawal with FDA-approved COX-2 inhibitor celecoxib. GFP-tagged TRAMP-C2 cells were co-implanted with prostate tissue in the dorsal chamber model and tumors were allowed to establish and vascularize. Tumor growth and angiogenesis were monitored in real-time using fluorescent intravital microscopy (IVM). Androgen withdrawal in mice was achieved using surgical castration or chemical hormonal ablation, alone or in combination with celecoxib (15 mg/kg, twice daily). Celecoxib alone decreased the growth of prostate tumors mostly by inducing mitotic failure, which resulted in increased apoptosis. Surprisingly, celecoxib did not possess significant angiostatic activity. Surgical or chemical castration prevented the growth of prostate tumors and this, on the other hand, was associated with disruption of the tumor vasculature. Finally, androgen withdrawal combined with celecoxib caused tumor regression through decreased angiogenesis and increased mitosis arrest and apoptosis. Celecoxib, a relatively safe COX-2-selective anti-inflammatory drug, significantly increases the efficacy of androgen withdrawal in vivo and warrants further investigation as a complement therapy for advanced prostate cancer.
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影响因子：
45.3
作者：
Antonarakis, Emmanuel S.;Heath, Elisabeth I.;Carducci, Michael A.
通讯作者：
Carducci, Michael A.
影响因子：
11.5
作者：
Fontana, Andrea;Galli, Luca;Bocci, Guido
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Bocci, Guido
影响因子：
3.2
作者：
Pruthi, Raj S;Wallen, Eric M
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Wallen, Eric M
影响因子：
8.8
作者：
Carles, J.;Font, A.;Mellado, B.;Domenech, M.;Gallardo, E.;Gonzalez-Larriba, J. L.;Catalan, G.;Alfaro, J.;del Alba, A. Gonzalez;Nogue, M.;Lianes, P.;Tello, J. M.
通讯作者：
Tello, J. M.
DOI：
10.1158/1940-6207.capr-09-0059
发表时间：
2010-01
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Zheng X;Cui XX;Gao Z;Zhao Y;Lin Y;Shih WJ;Huang MT;Liu Y;Rabson A;Reddy B;Yang CS;Conney AH
通讯作者：
Conney AH