Lev-Ari Shahar, Lichtenberg Dov, Arber Nadir
Department of Cancer Prevention, Tel Aviv Medical Center, Tel Aviv University, Israel.
Recent Pat Anticancer Drug Discov. 2008 Jan;3(1):55-62. doi: 10.2174/157489208783478720.
Celecoxib (Celebrex, Pfizer, NY, USA) is a worldwide top branded COX-2-specific inhibitor. It was shown to provide relief of arthritic pain and inflammation and has recently been under investigation for the prevention and treatment of cancer. However, recent studies showed that long term use of high doses of celecoxib is associated with an increased cardiovascular toxicity. We discovered that the addition of curcumin, a natural COX-2 inhibitor, to celecoxib synergistically (up to 1000%) augments the growth inhibitory effects of celecoxib in in-vitro and in-vivo models of arthritis and cancer, thus rendering effective action of the drug at up to tenfold lower dose. This may pave the way for a novel strategy to treat arthritis and cancer because its effect [1] can be achieved in the serum of patients receiving standard anti inflammatory or anti-neoplastic dosages of celecoxib, and [2] involves a regimen with a very low profile of side effects. Preliminary data suggest that the combination is not limited only to celecoxib and that addition of curcumin to other NSAIDs such as sulindac, synergistically augments neoplastic cell growth inhibition. Based on these finding we received an IRB approval to evaluate celecoxib+curcumin in patients with osteoarthritis, pancreatic cancer and metastatic CRC. We hope to complete these novel human clinical trials, in 12-18 months.
塞来昔布（西乐葆，辉瑞公司，美国纽约）是一种全球知名的环氧化酶-2（COX-2）特异性抑制剂。它已被证明可缓解关节炎疼痛和炎症，最近还在进行癌症预防和治疗方面的研究。然而，最近的研究表明，长期高剂量使用塞来昔布会增加心血管毒性。我们发现，在塞来昔布中添加天然COX-2抑制剂姜黄素，在体外和体内关节炎及癌症模型中，能协同增强（高达1000%）塞来昔布的生长抑制作用，从而使该药物在低至十分之一的剂量下仍能发挥有效作用。这可能为治疗关节炎和癌症开辟一种新策略，因为[1]在接受标准抗炎或抗肿瘤剂量塞来昔布的患者血清中就能实现其效果，且[2]所涉及的治疗方案副作用极小。初步数据表明，这种联合用药不仅限于塞来昔布，在其他非甾体抗炎药（如舒林酸）中添加姜黄素，也能协同增强对肿瘤细胞生长的抑制作用。基于这些发现，我们获得了机构审查委员会（IRB）的批准，以评估塞来昔布加姜黄素对骨关节炎、胰腺癌和转移性结直肠癌患者的疗效。我们希望在12至18个月内完成这些新型人体临床试验。
