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Chemopreventive action of Imatinib, a tyrosine kinase inhibitor in the regulation of angiogenesis and apoptosis in rat model of lung cancer

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Abstract

The present study explored the events of angiogenesis and apoptosis in 7,12-dimethyl benz(a)anthracene (DMBA)-induced lung cancer in rat and its chemoprevention with Imatinib, a receptor tyrosine kinase inhibitor. Further, it includes  lipopolysaccharide (LPS) mediating inflammation along with DMBA for the promotion of lung carcinogenesis. The animals received a single intratracheal instillation of DMBA (20 mg/kg body weight) in olive oil and LPS (0.6 mg/kg body weight) to induce tumors in 16 weeks. Besides morphology and histology of the lung tissues, RT-PCR, western blots, and immunofluorescence were performed for the expression of apoptotic and angiogenic proteins. Apoptosis was studied by mitochondrial Bcl-2/Bax ratio and staining with the dyes Acridine orange/ethidium bromide of the isolated Broncho epithelial cells. Also, mitochondrial membrane potential (ΔΨM) was studied by JC-1. The study revealed that the expression of VEGF, MMP-2, MMP-9, and the chemokine MCP-1 to be very high in DMBA and DMBA + LPS groups, while Bcl-2 also shows an elevated expression. These results were restored with Imatinib treatment. The pro-apoptotic proteins, Bax, Bad, Apaf-1, and Caspase-3 were highly diminished in DMBA and DMBA + LPS groups which were recovered with Imatinib treatment.

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Funding

The funding was provided by Indian Council of Medical Research (Grant No. 3/2/2/83/2011/NCD-III)

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Authors and Affiliations

  1. Department of Biophysics, Panjab University, Chandigarh, 160014, India

    Kulvinder Kumar, Preety Ghanghas & S. N. Sanyal

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  1. Kulvinder Kumar
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  2. Preety Ghanghas
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  3. S. N. Sanyal
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Correspondence to S. N. Sanyal.

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Kumar, K., Ghanghas, P. & Sanyal, S.N. Chemopreventive action of Imatinib, a tyrosine kinase inhibitor in the regulation of angiogenesis and apoptosis in rat model of lung cancer. Mol Cell Biochem 447, 47–61 (2018). https://doi.org/10.1007/s11010-018-3292-1

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