Synergistic antitumor activity of aspirin and erlotinib: Inhibition of p38 enhanced aspirin plus erlotinib‑induced suppression of metastasis and promoted cancer cell apoptosis

  • Authors:
    • Xiu Hu
    • Lin‑Wen Wu
    • Xu Weng
    • Neng‑Ming Lin
    • Chong Zhang
  • View Affiliations

  • Published online on: June 12, 2018     https://doi.org/10.3892/ol.2018.8956
  • Pages: 2715-2724
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Abstract

High‑dose erlotinib is effective for non‑small cell lung cancer patients with brain metastases. The aim of the present study was to investigate whether aspirin could increase the anti‑proliferative and anti‑metastatic effects of regular erlotinib treatment. The data demonstrated that combining aspirin with erlotinib significantly induced apoptosis and inhibited tumor cell proliferation in several human cancer types. Furthermore, aspirin plus erlotinib significantly induced the activation of E‑cadherin and suppression of p38. The data also indicated that the p38/E‑cadherin pathway may be involved in the apoptosis caused by the combination of aspirin and erlotinib. As p38 and E‑cadherin also serve a key role in epithelial‑to‑mesenchymal transition (EMT) and cancer metastasis, we hypothesized that the combination of aspirin and erlotinib may significantly inhibit tumor metastasis. First, aspirin plus erlotinib achieved potent inhibition of cancer cell migration and invasion, which are crucial for cancer metastasis. Next, the results demonstrated that aspirin plus erlotinib inhibited angiogenesis by suppressing endothelial cell migration and invasion. Moreover, it was confirmed that aspirin plus erlotinib exerted synergistic anti‑angiogenic effects. Finally, the synergistic anti‑proliferative and anti‑metastatic effects of the combination of aspirin with erlotinib were further validated in an A549 xenograft model in vivo. In conclusion, aspirin plus erlotinib may be an effective combination regimen for patients with metastatic cancer.
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August-2018
Volume 16 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Hu X, Wu LW, Weng X, Lin NM and Zhang C: Synergistic antitumor activity of aspirin and erlotinib: Inhibition of p38 enhanced aspirin plus erlotinib‑induced suppression of metastasis and promoted cancer cell apoptosis. Oncol Lett 16: 2715-2724, 2018
APA
Hu, X., Wu, L., Weng, X., Lin, N., & Zhang, C. (2018). Synergistic antitumor activity of aspirin and erlotinib: Inhibition of p38 enhanced aspirin plus erlotinib‑induced suppression of metastasis and promoted cancer cell apoptosis. Oncology Letters, 16, 2715-2724. https://doi.org/10.3892/ol.2018.8956
MLA
Hu, X., Wu, L., Weng, X., Lin, N., Zhang, C."Synergistic antitumor activity of aspirin and erlotinib: Inhibition of p38 enhanced aspirin plus erlotinib‑induced suppression of metastasis and promoted cancer cell apoptosis". Oncology Letters 16.2 (2018): 2715-2724.
Chicago
Hu, X., Wu, L., Weng, X., Lin, N., Zhang, C."Synergistic antitumor activity of aspirin and erlotinib: Inhibition of p38 enhanced aspirin plus erlotinib‑induced suppression of metastasis and promoted cancer cell apoptosis". Oncology Letters 16, no. 2 (2018): 2715-2724. https://doi.org/10.3892/ol.2018.8956