Curcumin inhibits cell proliferation and migration in NSCLC through a synergistic effect on the TLR4/MyD88 and EGFR pathways

Zhang,Lanfeng; Tao,Xingyu; Fu,Qiaofen; Ge,Chunlei; Li,Ruilei; Li,Zhen; Zhu,Ye; Tian,Hui; Li,Qiaolin; Liu,Min; Hu,Hongyan; Zeng,Baozhen; Lin,Zhuyin; Li,Chunyan; Luo,Rongcheng; Song,Xin

doi:10.3892/or.2019.7278

Curcumin inhibits cell proliferation and migration in NSCLC through a synergistic effect on the TLR4/MyD88 and EGFR pathways

Authors:
- Lanfeng Zhang
- Xingyu Tao
- Qiaofen Fu
- Chunlei Ge
- Ruilei Li
- Zhen Li
- Ye Zhu
- Hui Tian
- Qiaolin Li
- Min Liu
- Hongyan Hu
- Baozhen Zeng
- Zhuyin Lin
- Chunyan Li
- Rongcheng Luo
- Xin Song
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Affiliations: Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510315, P.R. China, Department of Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan 510118, P.R. China, Department of Medical Oncology, The Central Hospital of Hengyang, Hengyang, Hunan 421000, P.R. China, Department of Pathology, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan 510118, P.R. China, Central Laboratory of Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650051, P.R. China
Published online on: August 14, 2019 https://doi.org/10.3892/or.2019.7278
Pages: 1843-1855
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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