首页|曲古霉素A对结直肠癌组织5-氟尿嘧啶化疗敏感性的影响

曲古霉素A对结直肠癌组织5-氟尿嘧啶化疗敏感性的影响

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目的:探究5-氟尿嘧啶(5-Fluorouracil,5-FU)在结直肠癌(Colorectal Cancer,CRC)组织经曲古霉素A(Trichostatin A,TSA)(一种组蛋白去乙酰化酶抑制剂)处理,化疗敏感性的变化.方法:采用Lovo细胞株进行BALB/cA-nu裸小鼠荷瘤实验,按照对照组、5-FU组、TSA组、TSA→5-FU组(TSA预处理后给予 5-FU)以及TSA+5-FU组(TSA与 5-FU联合使用)随机分组并给予相应处理.记录各组移植瘤体积及质量,实验结束取移植瘤组织进行HE染色及Western Blot检测,比较各组裸鼠移植瘤体积、肿瘤抑制率以及胸苷酸合成酶(Thymidylate Synthase,TS)表达情况.结果:各化疗药物处理组移植瘤的体积显著小于对照组(p<0.05);TSA→5-FU组及TSA+5-FU组移植瘤的体积显著小于 5-FU组及TSA组(p<0.05),TSA→5-FU组与TSA+5-FU组之间、5-FU组与TSA组之间差异无统计学意义(p>0.05).各化疗药物处理组移植瘤生长抑制率显著高于对照组(p<0.05);TSA→5-FU组及TSA+5-FU组移植瘤生长抑制率显著高于 5-FU组及TSA组(p均<0.05),TSA→5-FU组与TSA+5-FU组之间、5-FU组与TSA组之间差异无统计学意义(p>0.05).各化疗药物处理组TS蛋白表达量显著低于对照组(p<0.05);TSA组、TSA→5-FU组及TSA+5-FU组移植瘤组织TS蛋白表达量显著低于 5-FU组(p<0.05),TSA→5-FU组与TSA+5-FU组移植瘤组织TS蛋白表达显著低于TSA组,TSA→5-FU组与TSA+5-FU组之间TS蛋白表达差异无统计学意义(p>0.05).结论:TSA可以提升 5-FU对CRC组织的化疗敏感性,可能与降低TS蛋白的表达量有关.
The Effect of Trichostatin A on the Sensitivity of Colorectal Cancer Tissues to 5-Fluorouracil Chemotherapy
Objective:To investigate the changes in the chemotherapy sensitivity of 5-fluorouracil(5-FU)in colorectal cancer(CRC)tissues treated with trichostatin A(TSA),a histone deacetylase inhibitor.Methods:BALB/cA-nu nude mouses tumor loading experiment is conducted using the Lovo cell line,and the tumor bearing nude mice are randomly divided into five different experimental groups:control group,5-FU group,TSA group,TSA→5-FU group(5-FU after TSA pretreatment),and TSA+5-FU group(TSA in combination with 5-FU),and corresponding treatments are given.The size and mass of each group's transplanted tumor is recorded on time,and at the end of the experiment,the tumor is taken for HE staining and Western Blot detection,and then compare the tumor volume,tumor inhibition rate,and protein expression of thymidine synthase(TS)among different groups of nude mice.Results:The size of transplanted tumors in each chemotherapy drug treatment group is smaller than that in the control group(p<0.05);the size of transplanted tumors in the TSA pretreatment group and TSA+5-FU group is reduced compared to the 5-FU group and the TSA group(p<0.05),and there is no statistically significant difference between the TSA→5-FU group and the TSA+5-FU group,as well as between the 5-FU group and the TSA group(p>0.05).The growth inhibition rate of transplanted tumors in each chemotherapy drug treatment group is higher than that in the control group(p<0.05);the TSA→5-FU group and TSA+5-FU group exhibits a higher growth inhibition rate of transplanted tumors compared to both the 5-FU group and the TSA group,and there is no statistically significant difference between the TSA→5-FU group and the TSA+5-FU group,as well as between the 5-FU group and the TSA group(p>0.05).The expression of TS protein in the drug treatment group is lower than that in the control group(p<0.05);the expression of TS protein in transplanted tumor tissues of TSA group,TSA→5-FU group,and TSA+5-FU group is lower than that of 5-FU group(p<0.05).The expression of TS protein in transplanted tumor tissues of TSA → 5-FU group and TSA+5-FU group is significantly lower than that of TSA group.There is no statistically significant difference in TS protein expression between TSA → 5-FU group and TSA+5-FU group(p>0.05).Conclusion:TSA can enhance the chemotherapy sensitivity of 5-FU to CRC tissue,and this effect may be related to the reduction of TS protein expression.

colorectal cancer5-fluorouraciltrichostatin Achemotherapy sensitivitythymidylate synthase

郭文莉、梁钢、马太芳、杨晓芳、李卿、肖虹

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山西医科大学汾阳学院 基础医学部,山西汾阳 032200

山西医科大学第一医院 病理科,山西 太原 030000

太原市血液中心,山西 太原 030001

结直肠癌 5-氟尿嘧啶 曲古霉素A 化疗敏感性 胸苷酸合成酶

2024

生物化工

生物化工

ISSN:
年,卷(期):2024.10(5)