ADD3可变剪接在结肠癌与正常组织间的差异表达

Differential expression of ADD3 splicing isoforms between colorectal cancer and normal mucosa tissues

目的:探讨内收蛋白3(ADD3)及其剪接体与结直肠癌(CRC)的关系。方法:Real-time PCR方法检测50对CRC组织、20对结直肠息肉组织、经5-氟尿嘧啶(5-FU)或奥沙利铂干预前后的SW480(低转移性)和SW620(高转移性)结肠癌细胞中ADD3-、ADD3-Ia和ADD3-Ib的表达量。用MTT检测细胞的活力,用划痕实验检测细胞的转移能力,用Transwell实验检测细胞的侵袭性。结果:CRC组织中ADD3与ADD3-Ib的表达量低于正常组织(P<0.01),ADD3-Ia/Ib比值高于正常组织(P<0.01);病理分组发现ADD3-Ia在T3-4组的表达量较T1-2组高(P<0.05)。结直肠息肉组织中ADD3、ADD3-Ia和ADD3-Ib的表达量低于正常组织(P<0.01)。SW620细胞中ADD3-Ia和ADD3-Ib的表达量低于SW480细胞(P<0.05),ADD3-Ia/Ib比值高于SW480(P<0.01);在经奥沙利铂和5-FU分别处理后,在SW620和SW480细胞活力、迁移和侵袭能力减弱,而ADD3、ADD3-Ia和ADD3-Ib的表达量均有不同程度增高。结论:CRC中ADD3-Ib和ADD3减少,并伴随ADD3-Ia/Ib比值升高。ADD3及其剪接体的改变可能跟CRC的侵袭能力有关。

AIM：To investigate the relationship between the expression of adducin 3（ ADD3） and its splicing isoforms and colorectal cancer（ CRC）.METHODS：The expression of ADD3,ADD3-Ia and ADD3-Ib in 50 pair of CRC tissues,20 pairs of colorectal polyp tissues,and 2 CRC cell lines SW480 and SW620 before and after oxaliplatin or fluorouracil intervention were detected by real-time PCR.The cell activity was determined by MTT assay,the cell migration ability was evaluated by wound-healing assay,and the cell invasion ability was measured by Transwell assay.RESULTS：The expression levels of ADD3 and ADD3-Ib were decreased in the CRC tissues as compared with the normal mucous（ P〈0.01）,and ADD3-Ia/Ib ratio was increased in the CRC tissues（ P〈0.01）.The expression level of ADD3-Ia was higher in T3-4 group than that in T1-2 group（ P〈0.05）.Reduced expression of ADD3,ADD3-Ia and ADD3-Ib in colorectal polyps was observed compared with the normal tissues（ P〈0.01）.Compared with the SW480 cells,the expression levels of ADD3-Ia and ADD3-Ib were lower（ P〈0.05） and the ADD3-Ia/Ib ratio was higher（ P〈0.01） in the SW620 cells.After treated with oxaliplatin or fluorouracil,the cell activity,migration and invasion in the SW620 and SW480 cells were weakened accompanied by the increases in the expression levels of ADD3,ADD3-Ia and ADD3-Ib to various certain extents.CONCLUSION：In CRC there is a tendency that ADD3-Ib reduction leads to ADD3 decrease,accompanied by an increased ADD3-Ia/Ib ratio.The expression changes of ADD3 and its splicing isoforms in the CRC may be relevant to its invasion ability.