Department of Chemotherapy, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Nanjing Medical University Affiliated Cancer HospitalNanjingP.R. China.
Department of Radiotherapy, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Nanjing Medical University Affiliated Cancer HospitalNanjingP.R. China.
Oncol Res. 2021 Sep 7;28(7):685-700. doi: 10.3727/096504020X15917007265498. Epub 2020 Jun 16.
Curcumol (Cur), isolated from the Traditional Chinese Medical plant , is the bioactive component of sesquiterpene reported to possess antitumor activity. However, its bioactivity and mechanisms against lung adenocarcinoma are still unclear. We investigated its effect on lung adenocarcinoma and elucidated its underlying molecular mechanisms. In vitro, Cur effectively suppressed proliferation, migration, and invasion of lung adenocarcinoma cells A549 and H460, which were associated with the altered expressions of signaling molecules, including p-AKT, p-PI3K, p-LRP5/6, AXIN, APC, GSK3 and p--catenin, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, Cur significantly induced cell apoptosis of A549 and H460 by promoting the expression of Bax, caspase 3, and caspase 9 and suppressing the expression of Bcl-2, and arrested the cell cycle at the G/G phase by lowering the levels of cyclin D1, CDK1, and CDK4. In vivo experiment revealed that Cur could inhibit lung tumor growth and lung metastasis, which were consistent with these in vitro results. In xenograft model mice, Cur strongly decreased tumor weight and tumor volume, which may be related to the downregulation of p-AKT and p-PI3K by immunofluorescence analysis. In addition, a lung metastasis model experiment suggested that Cur dramatically decreased the ratio of lung/total weight, tumor metastatic nodules, and the expressions of MMP-2 and MMP-9 in lung tissues compared with the control. Overall, these data suggested that the inhibitory activity of Cur on lung adenocarcinoma via the inactivation of PI3K/Akt and Wnt/-catenin pathways, at least in part, indicates that curcumol may be a potential antitumor agent for lung adenocarcinoma therapy.
姜黄素（Cur）是从传统中药植物中分离出来的生物活性成分，是具有抗肿瘤活性的倍半萜烯报告。然而，其对肺腺癌的生物活性及其机制仍不清楚。我们研究了其对肺腺癌的影响，并阐明了其潜在的分子机制。在体外，姜黄素有效抑制肺腺癌细胞 A549 和 H460 的增殖、迁移和侵袭，这与信号分子的改变表达有关，包括 p-AKT、p-PI3K、p-LRP5/6、AXIN、APC、GSK3 和 p--catenin、基质金属蛋白酶（MMP）-2 和 MMP-9。此外，姜黄素通过促进 Bax、caspase 3 和 caspase 9 的表达和抑制 Bcl-2 的表达，显著诱导 A549 和 H460 细胞凋亡，并通过降低细胞周期蛋白 D1、CDK1 和 CDK4 的水平将细胞周期阻滞在 G/G 期。体内实验表明，姜黄素能抑制肺肿瘤生长和肺转移，与体外实验结果一致。在异种移植模型小鼠中，姜黄素强烈降低肿瘤重量和肿瘤体积，这可能与免疫荧光分析中 p-AKT 和 p-PI3K 的下调有关。此外，肺转移模型实验表明，与对照组相比，姜黄素可显著降低肺/总重比、肿瘤转移结节以及肺组织中 MMP-2 和 MMP-9 的表达。总的来说，这些数据表明，姜黄素通过抑制 PI3K/Akt 和 Wnt/-catenin 通路对肺腺癌的抑制活性，至少部分表明姜黄素可能是肺腺癌治疗的一种潜在抗肿瘤药物。
