姜黄素引入酯键增韧基团对膀胱癌T24细胞靶向作用的体外研究
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国家自然科学基金(30860284);贵州省优秀科技教育人才省长专项资金[黔省专合字(2007)76号];贵州省教育厅自然科学类科研项目(黔教科:2007027)


In vitro study of curcumin-containing ester key toughening groups to T24 bladder cancer cells targeted role
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    摘要:

    目的:探讨姜黄素引入酯键增韧基团成为姜黄素前体化合物后靶向诱导膀胱癌T24细胞凋亡,为膀胱癌靶向治疗提供依据-方法:取不同浓度姜黄素前体化合物:叔丁氧羰基-苯丙氨酸酯姜黄素单脂(boc-phenylalanine-curcumin,BPC)及相同浓度的姜黄素对膀胱癌T24细胞及人主动脉平滑肌细胞(people aortic smooth muscle cells,HASMC)作用后,四甲基偶氮唑盐(MTT)法检测细胞抑制率,流式细胞仪检测细胞凋亡率,透视电镜观察BPC 20-40 μmol/L处理T24细胞后细胞超微结构的改变-结果:5~40 μmol/L BPC及姜黄素母体作用于膀胱癌T24细胞6~24 h后均明显抑制其增殖,呈时间剂量依赖,抑制率BPC:5.31%~59.34 %(P < 0.05);姜黄素:7.33%~63.59%(P < 0.05);对正常二聚体细胞HASMC的抑制作用BPC较姜黄素组明显降低(1.41%~12.34% vs 5.34%~36.59%),差异有统计学意义(P < 0.05);流式细胞仪分析5~40 μmol/L BPC及姜黄素作用于膀胱癌T24细胞24 h后,BPC诱导凋亡率:16.97%~47.12%(P < 0.05),姜黄素:19.21%~48.92%(P < 0.05);而对HASMC作用则较姜黄素明显减弱,BPC诱导凋亡率为:0.94%~3.27%,姜黄素组为:4.69%~11.35%,差异有统计学意义(P < 0.05)-透视电镜显示:经BPC作用后,T24细胞出现典型细胞凋亡的形态学特征-结论:姜黄素酯前体化合物BPC明显抑制膀胱癌T24细胞增殖-诱导其凋亡,而对正常二倍体细胞HASMC抑制作用降低,为姜黄素酯对肿瘤的靶向治疗研究提供新的依据-

    Abstract:

    Objective:To explore the apoptosis of bladder cancer cells T24 induced by curcumin precursor compounds,which were generated by introducing ester bond toughening groups and to provide a new foundation for treating bladder cancer. Methods:T24 bladder cancer cells and human aortic smooth muscle cells (HASMC) were treated with curcumin precursor compounds,boc-phenylalanine- curcumin (BPC),and curcumin,MTT assay was used to determine the cellular inhibition rate and flow cytometry was used to determine the apoptotic rate. Ultrastructural changes of T24 cells treated with 20 and 40 BPC μmol/L were by electronic microscopy. Results:BPC and curcumin precursor compounds at 5~40 μmol/L inhibited the proliferation of T24 bladder cancer cells following incubation for 6~24 h in a dose- and time-dependent manner. The inhibition rate of BPC was 5.31%~59.34 % (P < 0.05),and that of curcumin was 7.33%~63.59%(P < 0.05). Inhibition of normal HASMCs was reduced obviously compared with the curcumin group (the BPC group,1.41%~12.34% vs. the curcumin group,5.34%~36.59%,P < 0.05). There was a statistically significant difference(P < 0.05). Fow cytometry showed that,at 24 h,the apoptotic rate of T24 cells treated with 5~40 μmol/L BPC was 16.97%~47.12%(P < 0.05) and that of curcumin-treated cells was 19.21%~48.92% (P < 0.05). For HASMCs,the apoptotic rate of T24 cells treated with 5~40 μmol/L BPC was 0.94%~3.27%,and that of curcumin-treated cells was 4.69%~11.35%. There was a statistically significant difference (P < 0.05). Transmission electron microscopy showed that T24 cells treated with BPC exhibited morphological features typical of apoptosis. Conclusion:Curcumin ester compounds BPC can inhibit T24 bladder cancer cell proliferation and lead to apoptosis,but with no apparent effect on normal HASMCs. It may provide a new foundation for curcumin-based treatment of tumors.

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肖 峰,陈方敏,石家齐,任德帅,毕 磊,姜锡男,严 波,杨 艳,汤 磊,常傲霜.姜黄素引入酯键增韧基团对膀胱癌T24细胞靶向作用的体外研究[J].南京医科大学学报(自然科学版),2012,(5):645-649

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  • 收稿日期:2012-01-09
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