Department of Biophysics, Panjab University, Chandigarh, 160014, India.
Mol Cell Biochem. 2018 Oct;447(1-2):47-61. doi: 10.1007/s11010-018-3292-1. Epub 2018 Feb 16.
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 (ΔΨ) 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.
本研究探讨了血管生成和细胞凋亡在 7,12-二甲基苯并(a)蒽（DMBA）诱导的大鼠肺癌中的作用，以及 Imatinib（一种受体酪氨酸激酶抑制剂）对其的化学预防作用。此外，还包括脂多糖（LPS）介导的炎症与 DMBA 一起促进肺癌发生。动物接受单次气管内滴注 DMBA（20mg/kg 体重）和 LPS（0.6mg/kg 体重），16 周后诱导肿瘤。除了肺组织的形态学和组织学检查外，还进行了 RT-PCR、western blot 和免疫荧光分析，以检测凋亡和血管生成蛋白的表达。通过分离的支气管上皮细胞用吖啶橙/溴化乙锭染色研究细胞凋亡，通过 JC-1 研究线粒体膜电位（ΔΨ）。研究表明，VEGF、MMP-2、MMP-9 和趋化因子 MCP-1 在 DMBA 和 DMBA+LPS 组中的表达非常高，而 Bcl-2 的表达也升高。这些结果在 Imatinib 治疗后得到恢复。促凋亡蛋白 Bax、Bad、Apaf-1 和 Caspase-3 在 DMBA 和 DMBA+LPS 组中显著减少，在 Imatinib 治疗后得到恢复。
