辛二酰苯胺异羟肟酸对裸鼠人宫颈癌移植瘤的作用及其机制

Inhibition effects of SAHA on human cervical cancer cells in nude mice xenografts

目的观察辛二酰苯胺异羟肟酸(SAHA)对裸鼠人宫颈癌移植瘤生长的抑制作用,并对药物作用机制进行探讨。方法培养人宫颈癌SiHa细胞接种至20只裸鼠右下肢背侧根部皮下,15 d后将成瘤的18只裸鼠随机分3组:空白对照组、SAHA1组(25 mg/kg)、SAHA2组(50mg/kg),每组6只。连续4 d腹腔注射药物,间歇7 d,再连续给药4 d,1次/d。观察各组裸鼠宫颈癌移植瘤的生长情况,计算抑瘤率。免疫组化分析及Western blot方法检测各组移植瘤中的Bax及Bcl-2蛋白的表达。结果空白对照组抑廇率为0,SAHA1组为22.44%,SAHA2组为35.52%,2组比较差异有统计学意义(P<0.05)。用药后,SAHA2组裸鼠体质量低于空白对照组及SAHA1组(P<0.05)。SAHA1组与SAHA2组肿瘤体积均小于空白对照组,且SAHA2组小于SAHA1组(P均<0.05)。与空白对照组相比,SAHA1组与SAHA2组裸鼠肿瘤质量低,且SAHA2组低于SAHA1组,差异均有统计学意义(P均<0.05);免疫组化及蛋白印迹法检测结果显示,与空白对照组比较,SAHA1组、SAHA2组Bax蛋白均明显升高,Bcl-2蛋白均明显降低(P均<0.05)。而SAHA2组较SAHA1组变化更明显,差异有统计学意义(P均<0.05)。结论SAHA可以有效抑制人宫颈癌SiHa细胞裸鼠移植瘤的生长,Bax/Bcl-2相关的细胞凋亡是其抑癌机制之一。

Objective To observe the tumor growth inhibition effect of SAHA to human cervical cancer transplanted in nude mice and to discuss the mechanism .Methods Cultured human cancer cell lines in nude mice inoculated to 20 dorsal roots of the right lower limb subcutaneous , 15 d after the tumor will become 18 mice were randomly divided into three groups with each included 6 mice：blank control group, SAHA1 group （25 mg/kg）, SAHA2 group （50 mg/kg）.Consecutive 4d in-traperitoneal injection of drugs , intermittent 7 d, and then continuously administered 4 d, 1 times/d.Observe the growth of cancer xenografts in nude mice in each group , the inhibition rate was calculated .Immunohistochemistry and Western blot a-nalysis was used to detect the expression of tumor in each group Bax and Bcl-2 protein.Results Tumor suppression in blank control group was 0, SAHA1 group was 22.44%, SAHA2 group was 35.52% , the two groups was statistically significant difference （ P 〈0.05）.After treatment, SAHA2 group nude body mass were lower than the blank control group and SAHA 1 group （ P 〈0.05）.After treatment, SAHA1 group SAHA2 tumor volume was less than the blank control group , and the SA-HA2 group was less than SAHA1 group（ P 〈0.05）.Compared with the blank control group , SAHA1 group and SAHA2 nude mice＆#39;s tumors with low quality, and SAHA2 group lower than SAHA1 group, the differences were statistically significant （P 〈0.05）;in immunohistochemistry test and protein blotting method , compared with blank control group , tumor tissue Bax protein in SAHA1 group and SAHA2 group were significantly increased , Bcl-2 protein were significantly lowered （ P 〈0.05）.the changes in SAHA2 group were more obvious than SAHA1 group （ P 〈0.05）.Conclusion SAHA can inhibit human cancer xenograft SiHa cell growth , Bax/Bcl-2 -related apoptosis is one of the tumor suppressor mechanism .