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PNAS:新药物分子成功抑制肿瘤生长和转移

2014-07-17 佚名 生物谷

加州大学戴维斯分校,马萨诸塞大学和哈佛医学院研究人员成功将COX-2抑制剂如Celebrex与一个环氧化物水解酶(sEH)抑制剂组合起来,创建出一个新的潜在药物分子(PTUTB),此新药物能同时抑制肿瘤的生长和转移。通过将COX-2抑制剂和一个环氧化物水解酶(sEH)抑制剂组合,该药物PTUTB能控制血管生成(血管形成),限制了肿瘤的生长和扩散的能力。这项研究发表在PNAS杂志上。 加

加州大学戴维斯分校,马萨诸塞大学和哈佛医学院研究人员成功将COX-2抑制剂如Celebrex与一个环氧化物水解酶(sEH)抑制剂组合起来,创建出一个新的潜在药物分子(PTUTB),此新药物能同时抑制肿瘤的生长和转移。

通过将COX-2抑制剂和一个环氧化物水解酶(sEH)抑制剂组合,该药物PTUTB能控制血管生成(血管形成),限制了肿瘤的生长和扩散的能力。这项研究发表在PNAS杂志上。 

加州大学戴维斯分校杰出教授Bruce Hammock说:几年来,无论是单独使用还是两药合并联用,我们一直在研究COX抑制剂和sEH抑制剂对肿瘤的影响。我们惊讶地发现,新创造出的双重抑制剂比每种药物单独使用或合并联用使用更有效。通过将两个药物分子结合成一个新药物分子,我们得到了能更有效阻断肿瘤生长和转移的潜在新药物。

长期以来脂质信号一直与炎症,细胞迁移,增殖过程,高血压等有关,而COX和SEH酶控制了脂质信号。COX抑制剂能阻断诱导炎症和疼痛的脂质的生成,而SEH抑制剂是抗高血压,抗炎和镇痛的化合物。

这项研究中,科学家第一次联合COX-2抑制剂/sEH抑制剂,合成新药物(PTUTB)。然后他们在体外和在小鼠体内,测试双重抑制剂对人肺癌和乳腺癌的作用。他们发现PTUTB阻断血管生成,抑制血管内皮细胞的增殖(这是血管形成的关键)。这反过来限制肿瘤的生长和转移,降低肺癌和乳腺癌的生长。 

对于乳腺癌和肺癌,双重抑制剂可阻断血管生成,从而阻断实体肿瘤的生长。令人兴奋的是,相比于COX-2抑制剂,该新的组合药物有较小的副作用,没有心血管或胃肠道副反应。 
 
服用COX-2抑制剂后,会有心血管疾病风险,然而,SEH抑制剂与COX-2抑制剂合并后似乎能消除COX-2的副作用。

研究人员表示:虽然该研究专注于癌症方面,但双重抑制剂可能对其他疾病如黄斑变性也有一定作用。

原始出处:

Gupta R1, Dong Y1, Solomon PD1, Wettersten HI2, Cheng CJ3, Min JN4, Henson J5, Dogra SK6, Hwang SH7, Hammock BD7, Zhu LJ8, Reddel RR5, Saltzman WM9, Weiss RH10, Chang S4, Green MR11, Wajapeyee N12.Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A.Proc Natl Acad Sci U S A. 2014 Jul 14. pii: 201411370. [Epub ahead of print]


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    2014-10-20 drwjr
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