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- Title
Chemopreventive action of Imatinib, a tyrosine kinase inhibitor in the regulation of angiogenesis and apoptosis in rat model of lung cancer.
- Authors
Kumar, Kulvinder; Ghanghas, Preety; Sanyal, S. N.
- 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.
- Subjects
LUNG cancer; CHEMOPREVENTION; IMATINIB; PROTEIN-tyrosine kinases; NEOVASCULARIZATION
- Publication
Molecular & Cellular Biochemistry, 2018, Vol 447, Issue 1/2, p47
- ISSN
0300-8177
- Publication type
Article
- DOI
10.1007/s11010-018-3292-1