[1]陈瀛,郑克鸿,陈泽涛,等.干扰ADAM17表达可降低人结肠癌细胞对西妥昔单抗耐药[J].南方医科大学学报,2018,(11):1366.[doi:10.12122/j.issn.1673-4254.2018.11.15]
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干扰ADAM17表达可降低人结肠癌细胞对西妥昔单抗耐药()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年11期
页码:
1366
栏目:
出版日期:
2018-11-30

文章信息/Info

Title:
ADAM17 knockdown increases sensitivity of SW480 cells to cetuximad
作者:
陈瀛郑克鸿陈泽涛冯海湛方威黄宗海
关键词:
ADAM17结肠癌西妥昔单抗耐药
Keywords:
ADAM17 human colorectal cancer cetuximad drug resistance
DOI:
10.12122/j.issn.1673-4254.2018.11.15
摘要:
目的研究ADAM17的表达与结肠癌SW480细胞对西妥昔单抗耐药相关性。方法通过Western blot法检测结肠癌细胞 系ADAM17的表达情况,筛选出高表达ADAM17的结肠癌细胞株做为目标细胞株;采用siRNA片段干扰结肠癌细胞ADAM17 的表达,Western blot验证干扰效果;100 μg/mL的西妥昔单抗处理细胞24 h后,FITC/PI染色,流式细胞仪检测细胞凋亡情况; Transwell实验检测ADAM17不同表达状态下的结肠癌细胞的迁移能力;运用Western blot法,检测在ADAM17不同表达状态 下的结肠癌细胞EGFR、AKT的磷酸化水平。结果人结肠癌SW480 细胞株中ADAM17 表达较高(P<0.05)。siRNA-1 和 siRNA-2干扰片段可显著降低SW480株ADAM17表达(P<0.05)。ADAM17表达被干扰后的SW480细胞对西妥昔单抗敏感性 显著上升(P<0.05)。干扰ADAM17 表达后,在西妥昔单抗药物作用下SW480 细胞迁移能力显著降低(P<0.05)。干扰了 ADAM17 表达后,SW480 细胞实验组的p-EGFR、p-AKT较对照组组显著降低(P<0.001)。结论干扰ADAM17 表达可抑制 EGFR-AKT通路激活从而减少人结肠癌SW480细胞对西妥昔单抗耐药。
Abstract:
Objective To explore the association between expression of ADAM17 and cetuximad resistance in human colorectal cancer SW480 cells. Methods The expression of ADAM17 was detected using Western blotting in different human colorectal cancer cell lines, and the cells highly expressing ADAM17 were selected as the target cells. SW480 cells were transfected with ADAM17-siRNA 1 and ADAM17-siRNA 2 and the changes in the expression of ADAM17 protein were detected using Western blotting. SW480 cells were exposed to cetuximad for 24 h and the cell apoptosis was analyzed using flow cytometry. Transwell assay was used to examine the migration ability of SW480 cells with different expression levels of ADAM17; Western blotting was used to analyze the changes in the expressions of AKT signaling pathway-related proteins in the treated cells. Results The baseline expressions of ADAM17 were significantly higher in SW480 cells than in the other human colorectal cancer cell lines tested (P<0.05). Both ADAM17-siRNA 1 and 2 effectively reduced the expression of ADAM17 protein in SW480 cells. Knockdown of ADAM17 with siRNA 1 significantly increased the sensitivity of SW480 cells to tocetuximad (P<0.05), obviously inhibited the cell proliferation, migration and invasion, and significantly reduced the expressions of p-EGFR and p-AKT in the cells (P<0.001). Conclusion ADAM17 knockdown obviously inhibits EGFR-AKT signaling pathway and increases the sensitivity of SW480 cells to tocetuximad.

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