HOXA1基因反义寡核苷酸对结直肠癌细胞转移潜能的影响研究

Effect of HOXA1 gene antisense oligonucleotides on metastatic potential of colorectal cancer cells

目的探讨HOXA1基因反义寡核苷酸(ASODN)对结直肠癌HCT116细胞侵袭和迁移的影响及机制。方法将HCT116细胞分为:15 μmol/L的 HOXA1 ASODN处理组(ASODN组)、15 μmol/L N-ODN处理的无关对照组(N-ODN组)、15 μmol/L的HOXA1 SODN处理的正义对照组(SODN组)及正常对照组。Western blotting检测HOXA1、上皮型钙黏附素(E-cadherin)、神经型钙黏附素(N-cadherin)和波形蛋白(Vimentin)、磷脂酰肌醇3-激酶(PI3K)和磷酸化丝氨酸苏氨酸激酶(p-AKT)蛋白表达。MTT法检测细胞活力。Transwell小室检测细胞侵袭和迁移能力。对比四组上述各指标。结果与其他三组相比较,HOXA1 ASODN组可明显下调HOXA1、N-cadherin、Vimentin、PI3K和p-AKT蛋白表达,上调E-cadherin蛋白表达,抑制细胞活力、侵袭和迁移能力。结论 HOXA1基因反义寡核苷酸可明显降低结直肠癌细胞转移潜能,机制可能与抑制PI3K/AKT信号通路,从而逆转上皮间质转化有关。

Objective To investigate the effect and mechanism of HOXA1 antisense oligonucleotide (ASODN) on invasion and migration of colorectal cancer HCT116 cells. Methods HCT116 cells were divided into 15 umol/L HOXA1 ASODN treated group,15 μmol/L N-ODN treated unrelated control group,15 μmol/L HOXA1 SODN treated sense control group and normal control group. Western blotting was used to detect the expression of HOXA1,E-cadherin,N-cadherin,Vimentin,PI3K and p-AKT protein. MTT assay was used to detect cell viability. The cell invasion and migration ability was detected by Transwell chamber. Compare the above indicators in four groups. Results HOXA1 ASODN could significantly down-regulate the expression of HOXA1,N-cadherin,Vimentin,PI3K and p-AKT,up-regulate the expression of E-cadherin and inhibit cell viability,invasion and migration. Conclusion HOXA1 antisense oligonucleotides can significantly reduce the metastasis potential of colorectal cancer cells,which may be related to the inhibition of PI3K/AKT signaling pathway and the reversal of EMT.