Curcumin inhibits cell proliferation and migration in NSCLC through a synergistic effect on the TLR4/MyD88 and EGFR pathways
| Autor: | Rongcheng Luo, Hongyan Hu, Xin Song, Hui Tian, Zhen Li, Xingyu Tao, Baozhen Zeng, Lanfeng Zhang, Ruilei Li, Qiaolin Li, Ye Zhu, Qiaofen Fu, Zhuyin Lin, Liu Min, Chunyan Li, Chunlei Ge |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research Curcumin Epithelial-Mesenchymal Transition Lung Neoplasms Toll-like receptor 4/MyD88 Cell Antineoplastic Agents 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Humans non-small cell lung cancer Oncogene Dose-Response Relationship Drug Cell growth Cell migration General Medicine Articles Cell cycle Molecular medicine ErbB Receptors Gene Expression Regulation Neoplastic Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure cell proliferation Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Myeloid Differentiation Factor 88 Cancer research Female epidermal growth factor receptor Signal Transduction |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 |
| Popis: | Despite the increasing number of available therapeutic methods, the prognosis of non‑small cell lung cancer (NSCLC) remains poor. Furthermore, side effects are an important limiting factor in the treatment of NSCLC. Therefore, developing an efficacious, safe, affordable and easily accessible chemotherapeutic agent is necessary for NSCLC treatment. As a natural chemical produced by Zingiberaceae plants, curcumin exerts distinct antitumor effects on several tumor types. In the present study, curcumin was observed to inhibit not only cell proliferation and cell cycle transition, but also cell migration in NSCLC, as determined by a series of experiments (such as MTS assay, colony formation assay, flow cytometric analysis, Transwell migration assay and western blotting). Mechanistically, curcumin induced G2/M phase arrest by controlling cell cycle‑ and epithelial‑mesenchymal transition (EMT)‑related checkpoints. Furthermore, curcumin significantly inhibited the expression of Toll‑like receptor 4 (TLR4)/MyD88 and EGFR in a dose‑ and time‑dependent manner. Conversely, EGF reversed the inhibitory action of curcumin on TLR4/MyD88. In clinical specimens, TLR4 and MyD88 were highly expressed in NSCLC tissues, and a significant positive association was observed between TLR4 and MyD88 expression. These data suggested that curcumin may control the EGFR and TLR4/MyD88 pathways to synergistically downregulate downstream cell cycle‑ and EMT‑related regulators, in order to block cell proliferation and metastasis in NSCLC. These findings provide evidence for the clinical application of curcumin. |
| Databáze: | OpenAIRE |
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