Parthenolide inhibits human lung cancer cell growth by modulating the IGF‑1R/PI3K/Akt signaling pathway

Sun,Longhua; Yuan,Wenxin; Wen,Guilan; Yu,Bentong; Xu,Fei; Gan,Xin; Tang,Jianjun; Zeng,Qinghua; Zhu,Lanlan; Chen,Chuanhui; Zhang,Wei

doi:10.3892/or.2020.7649

Parthenolide inhibits human lung cancer cell growth by modulating the IGF‑1R/PI3K/Akt signaling pathway

Authors:
- Longhua Sun
- Wenxin Yuan
- Guilan Wen
- Bentong Yu
- Fei Xu
- Xin Gan
- Jianjun Tang
- Qinghua Zeng
- Lanlan Zhu
- Chuanhui Chen
- Wei Zhang
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Affiliations: Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Ultrasonography, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: June 17, 2020 https://doi.org/10.3892/or.2020.7649
Pages: 1184-1193

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Abstract

Lung cancer is the leading cause of cancer‑associated mortality worldwide. Parthenolide (PTL), a natural product extracted from the plant Tanacetum parthenium, (a flowering plant in the daisy family, Asteraceae) has been reported to inhibit cancer cell growth, including that of human lung cancer. However, the underlying mechanisms by which PTL exerts its anticancer effect have remained to be fully elucidated. In the present study, Cell Counting Kit‑8 and colony formation assays were used to assess the effect of PTL to inhibit cell proliferation, a wound‑healing assay was performed to assess cell migration and western blot analysis and PCR were employed to reveal the molecular mechanisms by which PTL inhibits human lung carcinoma cell growth. The results indicated that PTL substantially inhibited cell proliferation and migration in two lung cancer cell lines A549 and H1299. Mechanistically, the phosphorylation of insulin‑like growth factor 1 receptor (IGF‑1R), Akt and forkhead box O3α (FoxO3α) was blocked by PTL. Furthermore, IGF‑1‑induced Akt [protein kinase B or (PKB)] and FoxO3α phosphorylation were also inhibited by PTL treatment. In addition, PTL significantly suppressed lung cancer growth in a subcutaneous xenograft mouse model. Taken together, the present in vivo and in vitro results indicate that PTL may suppress lung cancer growth through inhibiting IGF‑1R‑mediated PI3K/Akt/FoxO3α signaling, suggesting that PTL may be an attractive candidate for the treatment of lung cancer.

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