摘要
目的:探讨丝裂霉素C(MMC)对瘢痕疙瘩成纤维细胞(FB)增殖和凋亡效应的影响及机制,为瘢痕疙瘩的治疗提供理论依据。方法:用MMC作用于体外培养的瘢痕疙瘩FB,MTT法测量细胞增殖情况;流式细胞术、光镜和透射电镜检测FB的周期分布、凋亡率和细胞形态学变化;通过RT-PCR、Western blotting检测cyclin D1和caspase-3的mRNA及蛋白表达水平。结果:MMC呈时间和剂量依赖性抑制瘢痕疙瘩FB增殖;MMC可改变细胞周期分布,使G0/G1期细胞比例增加,诱导FB凋亡,凋亡随剂量的增加而增加;MMC作用后cyclin D1的mRNA及蛋白表达减少,caspase-3的表达增加。结论:MMC可能是通过降低cyclin D1表达,促进caspase-3表达,改变细胞周期分布,抑制增殖诱导FB凋亡而发挥治疗瘢痕疙瘩作用。
AIM: To study the effects of mitomycin C (MMC) on proliferation and apoptosis of fibroblasts derived from keloid. METHODS: Using the cultured fibroblasts derived from keloid subjected to MMC, the proliferation of fibroblasts was detected by MTT. The flow cytometry, microscope and electron microscope were used for evaluation of cell cycles, apoptosis and modality. The expression of cyclin D1 and caspase-3 was detected by RT-PCR and western blotting. RESULTS: MMC inhibited proliferation of fibroblasts in a time- and concentration-dependent manner. MMC changed cell cycles and caused apoptosis in a dose-depended manner and increased the percentage of G0/G1 phase cells in fibroblasts. MMC decreased the expression of cyclin D1 and enhanced the expression of caspase-3. CONCLUSION: Changing theexpression of cyclin D1 and caspase-3, MMC may play a critical role in suppressing proliferation and inducing apoptosis of fibroblasts to prevention and cure keloid.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2007年第8期900-905,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics