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Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway

  • Authors:
    • Qin‑Fang Deng
    • Bo Su
    • Yin‑Min Zhao
    • Liang Tang
    • Jie Zhang
    • Cai‑Cun Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China, Central Laboratory, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, P.R. China
    Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 535-542
    |
    Published online on: November 18, 2015
       https://doi.org/10.3892/ol.2015.3945
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Abstract

The present study aimed to explore the role of integrin β1 and the relevant signaling pathways in acquired gefitinib resistance in non‑small cell lung cancer (NSCLC). The inhibitory effects of gefitinib, with or without LY294002, on cellular proliferation were evaluated by 3‑(4,5‑dimethylthiazol‑2‑yl) 2,5‑diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were analyzed by flow cytometry, while western blotting was used to evaluate the expression of EGFR, phosphorylated (phospho)‑EGFR, protein kinase B (Akt), phospho‑Akt, extracellular signal-regulated kinase (Erk) and phospho‑Erk. The gene expression profiles of PC9 and PC9/G cells were determined by DNA microarray. Integrin β1 was knocked down in PC9/G cells by transiently transfected short interfering RNA (siRNA). A scrambled siRNA sequence was used as a control. Apoptosis of transfected cells was determined by Annexin V‑phycoerythrin‑Cy5/propidium iodide staining. Sequencing products were amplified by nested PCR. The resistant index of PC9/G cells to gefitinib was ~138‑ to 256‑fold higher than that of PC9 cells, and this resistance was accompanied by significant increase in integrin β1 expression in PC9/G cells. Knockdown of integrin β1 with short hairpin RNA in PC9/G cells markedly inhibited proliferation and enhanced apoptosis in response to gefitinib, restoring the sensitivity of PC9/G cells gefitinib. Phosphoinositide 3-kinase (PI3K)/Akt activation was observed in PC9/G cells in the presence of gefitinib and the sensitivity of PC9/G cells to gefitinib was also able to be restored by PI3K/Akt pathway inhibitor LY294002. Finally, knockdown of integrin β1 significantly reduced the levels of phospho‑Akt. These findings suggest that integrin β1 signaling via the PI3K/Akt pathway may be a significant mechanism underlying gefitinib resistance, and may potentially present an alternative therapeutic target for the treatment of NSCLC unresponsive to EGFR inhibitors.
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Copy and paste a formatted citation
Spandidos Publications style
Deng QF, Su B, Zhao YM, Tang L, Zhang J and Zhou CC: Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway. Oncol Lett 11: 535-542, 2016.
APA
Deng, Q., Su, B., Zhao, Y., Tang, L., Zhang, J., & Zhou, C. (2016). Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway. Oncology Letters, 11, 535-542. https://doi.org/10.3892/ol.2015.3945
MLA
Deng, Q., Su, B., Zhao, Y., Tang, L., Zhang, J., Zhou, C."Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway". Oncology Letters 11.1 (2016): 535-542.
Chicago
Deng, Q., Su, B., Zhao, Y., Tang, L., Zhang, J., Zhou, C."Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway". Oncology Letters 11, no. 1 (2016): 535-542. https://doi.org/10.3892/ol.2015.3945
Copy and paste a formatted citation
x
Spandidos Publications style
Deng QF, Su B, Zhao YM, Tang L, Zhang J and Zhou CC: Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway. Oncol Lett 11: 535-542, 2016.
APA
Deng, Q., Su, B., Zhao, Y., Tang, L., Zhang, J., & Zhou, C. (2016). Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway. Oncology Letters, 11, 535-542. https://doi.org/10.3892/ol.2015.3945
MLA
Deng, Q., Su, B., Zhao, Y., Tang, L., Zhang, J., Zhou, C."Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway". Oncology Letters 11.1 (2016): 535-542.
Chicago
Deng, Q., Su, B., Zhao, Y., Tang, L., Zhang, J., Zhou, C."Integrin β1‑mediated acquired gefitinib resistance in non‑small cell lung cancer cells occurs via the phosphoinositide 3-kinase‑dependent pathway". Oncology Letters 11, no. 1 (2016): 535-542. https://doi.org/10.3892/ol.2015.3945
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