Department of Biophysics, Panjab University, Chandigarh 160014, India.
Mol Cell Biochem. 2013 Jan;372(1-2):101-12. doi: 10.1007/s11010-012-1451-3. Epub 2012 Sep 19.
This study explored the role of pro- and anti-inflammatory cytokines in dimethyl benz(a)anthracene (DMBA)-induced lung cancer and its subsequent correction with a COX-2 inhibitory NSAID, etoricoxib. A single dose of DMBA (20 mg/kg body weight) in 0.9 % NaCl administered intratracheally was used to induce tumors in the rat lungs in 20 weeks. The study of pro-inflammatory cytokines like IL-1β, TNF-α, and IFN-γ revealed their upregulation by DMBA administration and restoration of their levels toward normal by the treatment with etoricoxib, while the anti-inflammatory cytokine IL-2 was found to be down-regulated with carcinogen administration and corrected with etoricoxib treatment. Apoptosis was studied by mitochondrial Bcl-2/Bax ratio and staining with fluorescent dyes acridine orange/ethidium bromide. The results showed a decreased apoptotic level with DMBA which was corrected with etoricoxib. Also, mitochondrial membrane potential was studied using JC-1 and rhodamine-123, which are membrane permeant fluorescent dyes, and generate information about cells at lower and higher mitochondrial membrane potential (∆Ψ(M)). The results showed the presence of maximum number of cells with higher ∆Ψ(M) in the DMBA group and their number was considerably lowered in the other three groups.
本研究探讨了促炎和抗炎细胞因子在二甲基苯并(a)蒽（DMBA）诱导肺癌及其随后用 COX-2 抑制性 NSAID（依托考昔）纠正中的作用。用 0.9%NaCl 中的单剂量 DMBA（20mg/kg 体重）经气管内给药，在 20 周内诱导大鼠肺部肿瘤。促炎细胞因子如 IL-1β、TNF-α 和 IFN-γ 的研究表明，它们在 DMBA 给药后上调，并通过依托考昔治疗恢复正常水平，而抗炎细胞因子 IL-2 则在致癌剂给药后下调，并通过依托考昔治疗纠正。通过线粒体 Bcl-2/Bax 比值和吖啶橙/溴化乙锭荧光染料染色研究细胞凋亡。结果表明，DMBA 导致细胞凋亡水平降低，依托考昔可纠正这一现象。此外，还使用 JC-1 和罗丹明 123 研究线粒体膜电位，这两种是膜通透性荧光染料，可提供关于低和高线粒体膜电位（∆Ψ（M））下细胞的信息。结果表明，在 DMBA 组中存在最多数量具有较高 ∆Ψ（M）的细胞，而在其他三组中其数量明显降低。
