Yao Chih-Jung, Lai Gi-Ming, Chan Chin-Feng, Cheng Ann-Lii, Yang Ya-Yu, Chuang Shuang-En
Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan.
Int J Cancer. 2006 Feb 1;118(3):773-9. doi: 10.1002/ijc.21361.
Lovastatin (an HMG-CoA reductase inhibitor) and troglitazone (a PPAR-gamma agonist) have been intensively studied prospectively for their application in cancer treatment. However, clinical trials of lovastatin or troglitazone in cancer treatment resulted in only limited responses. To improve their efficacy, lovastatin and troglitazone have, respectively, been tried to combine with other anticancer agents with varied outcomes. In our study, we found a dramatic synergism between lovastatin and troglitazone in anticancer at clinically achievable concentrations. This synergism was found in far majority of cell lines tested including DBTRG 05 MG (glioblastoma) and CL1-0 (lung). This amazing synergism was accompanied by synergistic modulation of E2F-1 and p27(Kip1), which were reported to mediate the anticancer activities of lovastatin and troglitazone, respectively, and other cell cycle regulating proteins such as CDK2, cyclin A and RB phosphorylation status. With this dramatic combination effect of lovastatin and troglitazone, a promising regimen of cancer therapy may be materialized in the future.
洛伐他汀（一种HMG-CoA还原酶抑制剂）和曲格列酮（一种PPAR-γ激动剂）已针对其在癌症治疗中的应用进行了深入的前瞻性研究。然而，洛伐他汀或曲格列酮在癌症治疗中的临床试验仅产生了有限的反应。为提高它们的疗效，已分别尝试将洛伐他汀和曲格列酮与其他抗癌药物联合使用，结果各异。在我们的研究中，我们发现在临床可达到的浓度下，洛伐他汀和曲格列酮在抗癌方面具有显著的协同作用。在包括DBTRG 05 MG（胶质母细胞瘤）和CL1-0（肺癌）在内的绝大多数测试细胞系中都发现了这种协同作用。这种惊人的协同作用伴随着E2F-1和p27（Kip1）的协同调节，据报道它们分别介导洛伐他汀和曲格列酮的抗癌活性，以及其他细胞周期调节蛋白，如CDK2、细胞周期蛋白A和RB磷酸化状态。凭借洛伐他汀和曲格列酮这种显著的联合效应，未来可能实现一种有前景的癌症治疗方案。
