Parthenolide inhibits human lung cancer cell growth by modulating the IGF‑1R/PI3K/Akt signaling pathway.
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.
['Sun|Longhua|L|', 'Yuan|Wenxin|W|', 'Wen|Guilan|G|', 'Yu|Bentong|B|', 'Xu|Fei|F|', 'Gan|Xin|X|', 'Tang|Jianjun|J|', 'Zeng|Qinghua|Q|', 'Zhu|Lanlan|L|', 'Chen|Chuanhui|C|', 'Zhang|Wei|W|']
D000818:Animals D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D000071316:Forkhead Box Protein O3 D006801:Humans D007334:Insulin-Like Growth Factor I D008175:Lung Neoplasms D008297:Male D051379:Mice D019869:Phosphatidylinositol 3-Kinases D010766:Phosphorylation D051057:Proto-Oncogene Proteins c-akt D017526:Receptor, IGF Type 1 D012717:Sesquiterpenes D015398:Signal Transduction D023041:Xenograft Model Antitumor Assays
parthenolide lung cancer proliferation migration IGF-1R