摘要
目的探讨结直肠癌组织中CCDC12蛋白表达与肿瘤细胞化疗效果的关系及意义。方法留取84例结直肠癌手术患者的肿瘤及癌旁正常肠黏膜的石蜡组织及新鲜组织,免疫组化技术检测CCDC12蛋白、多药耐药蛋白1(MRP-1)、P-糖蛋白(P-gp)、生存素(Survivin)、凋亡酶激活因子-1(Apaf-1)的表达情况;噻唑蓝(MTT)法检测氟尿嘧啶(5-Fu)、顺铂(CDDP)、奥沙利铂(L-OHP)对肿瘤细胞的抑制作用。另取20例结直肠癌患者的肿瘤及癌旁正常肠黏膜新鲜标本,蛋白印迹法(Western blotting)检测CCDC12、MRP-1、P-gp、Survivin、Apaf-1的表达情况。结果免疫组化结果显示CCDC12、MRP-1、P-gp、Survivin在结直肠癌组织中表达均明显高于癌旁正常肠黏膜,Apaf-1在结直肠癌组织中表达降低(均P<0.05)。5-Fu、L-OHP对CCDC12阳性表达的结直肠癌细胞抑制率低于阴性表达者(均P<0.05),而CDDP对肿瘤细胞的抑制作用与CCDC12表达无明显关系(P>0.05)。5-Fu对结直肠癌细胞的抑制情况与MRP-1、P-gp表达有关;CDDP对肿瘤细胞的抑制情况与Survivin有关;L-OHP对肿瘤细胞的抑制作用与Survivin、Apaf-1有关(均P<0.05)。相关分析显示,结直肠癌组织中CCDC12蛋白与P-gp、Survivin均呈正相关,与Apaf-1呈负相关(均P<0.05)。Western blot结果与免疫组化相符。结论 CCDC12蛋白在结直肠癌组织中表达增高并与化疗药物的效果有关,CCDC12蛋白参与了结直肠癌的耐药形成并可能成为耐药性逆转的靶蛋白。
Objective To investigate the correlation and significance between expression of CCDC12 protein and therapeutic effects of chemotherapy on colorectal cancer. Methods The expressions levels of CCDC12, MRP-1, P-gp, Survivin, Apaf-1 proteins were detected by immunohistochemistry in 84 cases of colorectal cancer （tissue specimens）. The inhibitory effects of chemotherapeutics 5-Fu, CDDP, L-OHP on tumor cells were detected by MTT assay. Moreover the expressions levels of CCDC12,MRP-1,P-gp,Survivin,Apaf-1 proteins in fresh tissues of 20 cases of colorectal cancer and mucous membrane tissues beside cancer were detected by Western Blot assay. Results The expressions levels of CCDC12, MRP-1,P-gp, Survivin proteins in colorectal cancer tissues were obviously higher than those in normal intestine mucous membrane,however, the expression levels of Apaf-1 were decreased in colorectal cancer tissues （P〈0. 05）. The inhibitory rates of 5-Fu, L-OHP on tumor cells with positive expression of CCDC12 were significantly lower than those with negative expression of CCDC12 （P〈0. 05）,but there was no obvious correlation between the inhibitory effects of CDDP on tumor cells and expression of CCDC12 （P 〉0. 05）. The inhibition effects of 5-Fu on tumor cells were related with the expressions of MRP-1 and P-gp proteins, and the inhibition effects of CDDCP on tumor celles were related with expressions of Survivin protein,moreover, the inhibition effects of L-OHP were correlated to expressions of Survivin,Apaf-1 proteins. The correlation analysis showed that the expressions of CCDC12 protein in colorectal cancer tissues were positively correlated to those of P-gp, Survivin,however,which were negatively correlated to those of Apaf-1 （P 〈0. 05）. Conclusion The expression levels of CCDC12 protein are increased in colorectal cancer tissues,which is correlated to the therapeutic effects of chemotherapy on colon cancer. Moreover CCDC12 may be involved in chemotherapeutics resistance,which may be a potential target protein fo
出处
《河北医药》
CAS
2017年第20期3064-3067,共4页
Hebei Medical Journal
