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Tropical Journal of Pharmaceutical Research

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Inhibition of platelet-tumour cell interaction with ibrutinib reduces proliferation, migration and invasion of lung cancer cells

Zhiqiang Fu, Haifeng Wang, Yi Zhou, Qi Zhou

Abstract


Purpose: To investigate the pharmacological role of the Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, in tumour cell-platelet crosstalk in lung cancer.
Methods: Human lung cancer cells A549 were treated with ibrutinib or DMSO. mRNA expression was assessed using reverse transcription-quantitative polymerase chain reaction (RT-PCR), and while western blotting was used to determine protein expression levels. Small interfering RNA (siRNA) transfection was performed to suppress the expression of galectin-3. Colony formation and Transwell® assays were used to determine cell viability, cell invasiveness and migratory ability.
Results: Co-culture of A549 cells and platelets induced activation of BTK/PLCγ2 signalling and subsequent release of PDGF, VEGF and TGFβ1 from de-granulated platelets. However, knocking down of galectin-3 inhibited A549-induced platelet activation. Conversely, platelet activation upregulated the expression of galectin-3 via the release of PDGF. Moreover, ibrutinib significantly (p < 0.05) inhibited cell viability, migration, and invasion.
Conclusion: These results suggest that ibrutinib may be a novel therapeutic treatment for lung cancer.

Keywords: Bruton tyrosine kinase, Ibrutinib, Lung cancer, Platelet




http://dx.doi.org/10.4314/tjpr.v17i4.4
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