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Article

Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells

  • Authors:
    • Qing Fang
    • Yuyin Zhu
    • Qilai Wang
    • Meijun Song
    • Guosheng Gao
    • Zhiming Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary Medicine, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315000, P.R. China, Department of Emergency Medicine, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315000, P.R. China, Department of Laboratory, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315000, P.R. China
  • Pages: 507-516
    |
    Published online on: October 18, 2018
       https://doi.org/10.3892/ijmm.2018.3939
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Abstract

Safe, affordable and efficacious agents are urgently required for cancer prevention. Sesamin, a lipid‑soluble lignan from sesame (Sesamum indicum) displays anticancer activities through an unknown mechanism. In the present study, the anticancer activity of sesamin via cyclooxygenase 2 (COX2) was investigated in lung cancer. Quantitative polymerase chain reaction was performed to determine the mRNA expression levels of COX2 in cells, while western blot analysis was used to determine its protein expression levels. Cell proliferation was evaluated by Cell Counting Kit‑8 assay, while apoptosis and cell cycle analyses were conducted by flow cytometry. The results indicated that COX2 expression was upregulated in lung cancer cell lines compared with human normal lung epithelial cell line BEAS‑2B and sesamin was demonstrated to decrease the levels of COX2, inhibit the proliferation of lung cancer cells and promote their apoptosis in a concentration‑dependent manner. Furthermore, decreased COX2 expression potentiated sesamin‑induced apoptosis and G1‑phase arrest, which was correlated with the suppression of gene products associated with cell apoptosis (Bcl‑2 and Bax) and the cell cycle (cyclin E1). In addition, cotreatment with the COX2 inhibitor CAY10404 and sesamin downregulated the expression of downstream molecules of COX2 [including interleukin (IL)1β, IL6 and tumor necrosis factor α] compared with CAY10404 or sesamin alone. Furthermore, cotreatment with sesamin and CAY10404 markedly reduced the levels of phosphorylated protein kinase B (pAkt) and phosoinositide 3 kinase (PI3K) in three lung cancer cell lines. PI3K expression was observed to be under the control of COX2, possibly forming a negative feedback loop. In addition, PI3K depletion induced apoptosis and G1‑phase arrest in A549 cells. These results suggested that sesamin blocked the pAkt‑PI3K signaling pathway by downregulating the expression of COX2, therefore resulting in cell cycle arrest and increased apoptosis in vitro. In conclusion, inhibition of COX2 increased the sensitivity of lung cancer cells to sesamin by modulating pAkt‑PI3K signaling. These results may aid the development of more selective agents to overcome cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Fang Q, Zhu Y, Wang Q, Song M, Gao G and Zhou Z: Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells. Int J Mol Med 43: 507-516, 2019.
APA
Fang, Q., Zhu, Y., Wang, Q., Song, M., Gao, G., & Zhou, Z. (2019). Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells. International Journal of Molecular Medicine, 43, 507-516. https://doi.org/10.3892/ijmm.2018.3939
MLA
Fang, Q., Zhu, Y., Wang, Q., Song, M., Gao, G., Zhou, Z."Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells". International Journal of Molecular Medicine 43.1 (2019): 507-516.
Chicago
Fang, Q., Zhu, Y., Wang, Q., Song, M., Gao, G., Zhou, Z."Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells". International Journal of Molecular Medicine 43, no. 1 (2019): 507-516. https://doi.org/10.3892/ijmm.2018.3939
Copy and paste a formatted citation
x
Spandidos Publications style
Fang Q, Zhu Y, Wang Q, Song M, Gao G and Zhou Z: Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells. Int J Mol Med 43: 507-516, 2019.
APA
Fang, Q., Zhu, Y., Wang, Q., Song, M., Gao, G., & Zhou, Z. (2019). Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells. International Journal of Molecular Medicine, 43, 507-516. https://doi.org/10.3892/ijmm.2018.3939
MLA
Fang, Q., Zhu, Y., Wang, Q., Song, M., Gao, G., Zhou, Z."Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells". International Journal of Molecular Medicine 43.1 (2019): 507-516.
Chicago
Fang, Q., Zhu, Y., Wang, Q., Song, M., Gao, G., Zhou, Z."Suppression of cyclooxygenase 2 increases chemosensitivity to sesamin through the Akt‑PI3K signaling pathway in lung cancer cells". International Journal of Molecular Medicine 43, no. 1 (2019): 507-516. https://doi.org/10.3892/ijmm.2018.3939
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