孔雀绿在口腔癌和肺癌细胞株中的抗癌作用及其机制研究

发布时间：2018-03-10 08:54

本文选题：孔雀绿　切入点：头颈癌　出处：《南京医科大学》2016年博士论文　论文类型：学位论文

【摘要】：背景孔雀绿广泛用于各种染料工业及水厂养殖业,因为其潜在的致癌性,孔雀绿从未被应用于医学方面或者制药方面的考虑。在一次药物筛选过程中,偶然中发现孔雀绿可能具有潜在的抑制肿瘤细胞生长的能力,能显著抑制头颈癌细胞株的增殖,这在之前的文献中未见相关报道。本研究的目的在于确定孔雀绿是否具有抗癌作用并探讨这种作用可能的机制。方法我们将5种肺癌细胞株和2种口腔癌细胞株暴露于含有一系列浓度的孔雀绿的完全培养基中,检测其增殖能力,分析孔雀绿可能对这些细胞产生的作用。将细胞暴露于孔雀绿24小时后,MTT检测细胞的增殖有无受到影响,流式细胞仪检测细胞周期的变化,并运用Western blot进行细胞周期及凋亡相关蛋白的检测。明确孔雀绿对细胞株产生抑制增殖作用后,运用裸鼠肺癌模型来检测孔雀绿在体实验的效果。结果孔雀绿具有明显的抑癌效果,其IC50值在0.1μM到0.6 gM之间。在大部分细胞除了A549细胞外,孔雀绿造成了大部分细胞的凋亡,并且Western blot显示cleaved PARP明显增加；而对于A549细胞,孔雀绿则造成了它的G1期阻滞现象,值得研究的是,这种G1期的阻滞伴随着RB总量的减少,细胞周期相关蛋白CyclinE2的增加。而在裸鼠模型中,孔雀绿的抑癌作用也相当明显。结论孔雀绿对于肿瘤细胞的增殖具有抑制作用,这种作用可能通过促进细胞的凋亡及G1期阻滞来达到,而这种G1期阻滞非通过经典的RB途径,这需要下一步的研究发现机制,为孔雀绿作为抑制恶性肿瘤的一个化合物的下一步研究提供理论依据。
[Abstract]:Background malachite green is widely used in various dyestuff industries and waterworks, because of its potential carcinogenicity, malachite green has never been used for medical or pharmaceutical purposes. Malachite green may have the potential to inhibit the growth of tumor cells and significantly inhibit the proliferation of head and neck cancer cells. The purpose of this study was to determine whether malachite green has anticancer effect and to explore the possible mechanism of this effect. Methods We have five lung cancer cell lines and two oral cancer cell lines. Exposed to a complete medium containing a series of malachite green, After 24 hours of malachite green exposure to malachite green, MTT assay showed whether the proliferation of cells was affected, flow cytometry was used to detect the changes of cell cycle. Western blot was used to detect cell cycle and apoptosis-related protein. The effect of malachite green in vivo was detected by using lung cancer model in nude mice. Results malachite green had obvious inhibitory effect, its IC50 value ranged from 0. 1 渭 M to 0. 6 mm. In most cells, except A549 cells, malachite green caused apoptosis in most cells. Western blot showed that cleaved PARP increased significantly, but malachite green caused G1 phase arrest in A549 cells. In nude mice model, malachite green has a significant inhibitory effect on cancer. Conclusion malachite green can inhibit the proliferation of tumor cells. This effect may be achieved by promoting cell apoptosis and G1 phase arrest, which is not via the classical RB pathway, which requires further research and discovery of the mechanism. It provides a theoretical basis for the further study of malachite green as a compound inhibiting malignant tumor.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R734.2;R739.8

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