尼妥珠单抗降低BRCA1蛋白表达提高大肠癌SW480细胞对伊立替康敏感性的研究  

Nimotuzumab down-regulates BRCA1 expression and enhances sensitivity of colon cancer cells to irinotecan treatment

作　　者：孙晓东[1] 

机构地区：[1]浙江大学医学院附属邵逸夫医院普外科,杭州310016

出　　处：《浙江医学》2012年第13期1103-1106,共4页Zhejiang Medical Journal

摘　　要：目的探讨尼妥珠单抗联合伊立替康对大肠癌细胞增殖的抑制作用及可能机制。方法100tJg／ml尼妥珠单抗、5ug／ml伊立替康单独和联合作用大肠癌SW480细胞24、48h后，采用MTT法检测细胞增殖，流式细胞仪检测细胞凋亡。Westernblot技术检测ERKl／2、pERKl／2及乳腺癌易感基因1（BRCAl）蛋白的表达水平。结果尼妥珠单抗和伊立替康联合作用SW480细胞48h后，其细胞增殖抑制与其他各组相比，差异有统计学意义（P〈0．01）。伊立替康和尼妥珠单抗单药作用24h后，未能明显诱导SW480细胞凋亡，但作用48h后伊立替康诱导的凋亡率为16．01％，而尼妥珠单抗组的细胞凋亡仍不明显。尼妥珠单抗联合伊立替康作用24h后，也未能明显诱导SW480细胞凋亡，而48h后，细胞凋亡率明显增多，可达26．34％，与其他各组相比，差异有统计学意义（尸〈O．01）。ERK1／2在对照组和各处理组中的表达无变化，而pERKl／2在对照组和伊立替康组的表达无变化，在尼妥珠单抗组和尼妥珠单抗＋伊立替康组的表达明显降低。伊立替康单药处理SW480细胞后，BRCAl蛋白表达量增加，尼妥珠单抗单药处理后BRCAl表达也有所增加。但尼妥珠单抗与伊立替康联合作用后，SW480细胞的BRCAl蛋白表达明显降低。结论尼妥珠单抗与伊立替康能协同抑制大肠癌细胞增殖，其机制可能是降低BRCAl蛋白的表达。Objective To investigate the effects of nimotuzumab combined with irinotecan on colon cancer cells. Methods Colon cancer SW480 cells were treated with nimotuzumab, irinotecan or nimotuzumab combined with irinotecan for 24h and 48h, respectively. Growth inhibition rate of SW480 cells were measured by MTT assay, apoptosis was detected by flow cytometery, the expressive levels of ERK1/2, pERK1/2 and BRCA1 were detected by Western blot. Results The growth inhibition rate and apoptosis rate of colon cancer SW480 cells treated by nimotuzumab combined with irinotecan for 48h were significantly higher with those of other groups（ both P〈O.01 ）. There were no changes in ERKt/2 expression in all groups and no changes in pERK1/2 expression in control and irinotecan groups, however, pRK1/2 was decreased in nimotuzumab group and nimotuzumab com- bined with irinotecan group. The expressive levels of BRCA1 were elevated in nimotuzumab and irinotecan groups, but were de- creased in nimotuzumab combined with irinotecan group. Conclusion Nimotuzumab enhances the sensitivity of colon cancer cells to irinotecan treatment, which may be associated with the down-regulation of BRCA1 expression in colon cancer cells.

关 键 词：大肠癌 尼妥珠单抗 伊立替康 乳腺癌易感基因1 

分 类 号：R971.1[医药卫生—药品]