Curcumol potentiates celecoxib-induced growth inhibition and apoptosis in human non-small cell lung cancer.
Curcumol potentiates celecoxib-induced growth inhibition and apoptosis in human non-small cell lung cancer.
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姜黄酚增强塞来昔布诱导的人非小细胞肺癌生长抑制和细胞凋亡
DOI：
10.18632/oncotarget.23308
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发表时间：
2017-12-29
期刊：
影响因子：
--
通讯作者：
Zhuang H
中科院分区：
文献类型：
--
作者：
Cai F;Chen M;Zha D;Zhang P;Zhang X;Cao N;Wang J;He Y;Fan X;Zhang W;Fu Z;Lai Y;Hua ZC;Zhuang H
靶向多种信号传导途径的组合疗法可以提供优于单一疗法的改善的治疗反应。塞来昔布和莪术醇是两种高度疏水的药物，由于其水溶性差而显示出生物利用度问题。在本研究中，我们评估了塞来昔布和莪术醇单独和联合使用对细胞增殖，侵袭，迁移，细胞周期和凋亡诱导的非小细胞肺癌（NSCLC）细胞在体外和体内实验。我们的数据显示，使用低浓度塞来昔布和莪术醇的联合治疗的敏感性高于塞来昔布或莪术醇单独使用。抑制NF-κ B转录活性、激活caspase-9/caspase-3、细胞周期G1期阻滞、抑制存活MAPK和PI3 K/AKT信号通路参与了该联合疗法诱导凋亡的协同效应。此外，塞来昔布单用或与莪术醇联合使用通过抑制FAK和基质金属蛋白酶-9活性抑制NSCLC细胞迁移和侵袭。此外，通过尾静脉注射，联合治疗减少了异种移植小鼠模型中的肿瘤体积和重量，并显著减少了肺组织中的肿瘤转移结节。我们的研究结果证实并提供了塞来昔布和/或莪术醇对NSCLC细胞的显著抗增殖活性的机制见解，这为进一步详细的临床前和潜在的临床研究提供了理论基础。
Combinatorial therapies that target multiple signaling pathways may provide improved therapeutic responses over monotherapies. Celecoxib and curcumol are two highly hydrophobic drugs which show bioavailability problems due to their poor aqueous solubility. In the present study, we evaluated the effects of celecoxib and curcumol alone and in combination on cell proliferation, invasion, migration, cell cycle and apoptosis induction in non-small cell lung cancer (NSCLC) cells using in vitro and in vivo experiments. Our data showed that the sensitivity of a combined therapy using low concentration of celecoxib and curcumol was higher than that of celecoxib or curcumol alone. Suppression of NF-κB transcriptional activity, activation of caspase-9/caspase-3, cell cycle G1 arrest, and inhibition of survival MAPK and PI3K/AKT signaling pathway contributed to the synergistic effects of this combination therapy for induction of apoptosis. Additionally, either celecoxib alone or in combination with curcumol inhibited NSCLC cell migration and invasion by suppressing FAK and matrix metalloproteinase-9 activities. Furthermore, the combined treatment reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. Our results confirm and provide mechanistic insights into the prominent anti-proliferative activities of celecoxib and/or curcumol on NSCLC cells, which provide a rationale for further detailed preclinical and potentially clinical studies of this combination for the therapy of lung cancer.
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影响因子：
9.2
作者：
Gupta, Subash C.;Kim, Ji Hye;Prasad, Sahdeo;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.
影响因子：
11.2
作者：
Han, C;Leng, J;Wu, T
通讯作者：
Wu, T
影响因子：
3.4
作者：
Chen, Likun;He, Youjian;Wei, Weidong
通讯作者：
Wei, Weidong
影响因子：
2.6
作者：
Gaikwad, Amos;Prchal, Josef T.
通讯作者：
Prchal, Josef T.
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影响因子：
5
作者：
Chen, Xi;Zong, Chuanjie;Qi, Yun
通讯作者：
Qi, Yun