Title外源性HER2基因导入未能提高HER2阴性胃癌细胞系对曲妥珠单抗的敏感性
Other TitlesIntroduction of exogenous HER2 fails to improve the sensitivity of HER2-negative gastric cancer cell lines to trastuzumab
Authors张朦琦
陈祖华
杨菁
章程
沈琳
高静
Affiliation北京大学肿瘤医院暨北京市肿瘤防治研究所消化肿瘤内科恶性肿瘤发病机制及转化研究教育部重点实验室
Keywords外源性HER2
HER2阴性胃癌
曲妥珠单抗
exogenous HER2
HER2-negative gastric cancer
trastuzumab
Issue Date2019
Publisher基础医学与临床
Abstract目的探索外源性人表皮生长因子受体2(HER2)基因导入使HER2阴性胃癌细胞系对曲妥珠单抗敏感性的影响。方法构建人HER2真核表达载体,转染人HER2阴性胃癌细胞系(HGC-27和MGC803)及正常胃上皮细胞GES1(作为对照),细胞免疫荧光与蛋白印迹(Western blot,WB)检测HER2表达及下游信号通路变化,CCK-8法检测细胞增殖活性。结果 HER2阴性胃癌细胞及正常细胞导入外源性HER2后,HER2蛋白表达明显上调,但磷酸化HER2(pHER2)表达无变化。外源性HER2基因导入后,HER2阴性细胞对曲妥珠单抗的敏感性无增加,甚至有下降趋势。此外,外源性HER2基因导入后,HER2下游PI3K/AKT、MAPK通路不但未激活,反而受到明显抑制。结论外源性HER2基因导入无法使HER2阴性胃癌从曲妥珠单抗治疗中获益,主要原因可能是外源性HER2基因无法使其下游PI3K/AKT、MAPK通路激活,外源性和内源性HER2发挥的作用可能不同,有待后续深入研究。
Objective To explore the feasibility of HER2-negative gastric cancer cell lines benefiting from trastuzumab treatment after exogenous HER2 gene introduction. Methods Human HER2 eukaryotic expression vector was constructed and transfected into human gastric cancer cell lines(HGC-27 and MGC803) and normal gastric epithelial cell GES1(as control). Immunofluorescence and Western blot were used to detect HER2 and its downstream signaling pathways, and CCK-8 assay was used to measure the viability of cells. Results After the introduction of exogenous HER2 into HER2-negative gastric cancer cells and normal cells, HER2 was significantly upregulated rather than phosphorylated HER2(pHER2). Also, the sensitivity of HER2-negative cells to trastuzumab wasn't increased after the introduction of exogenous HER2. In addition, PI3 K/AKT and MAPK pathways were not activated but significantly inhibited after the introduction of exogenous HER2. Conclusions Exogenous HER2 introduction cannot benefit HER2-negative gastric cancer from trastuzumab treatment. The main reason might be that exogenous HER2 does not activate its downstream PI3 K/AKT and MAPK pathways. The role of exogenous and endogenous HER2 may be different,which will be explored in further study.
URIhttp://hdl.handle.net/20.500.11897/560778
ISSN1001-6325
DOI10.16352/j.issn.1001-6325.2019.04.007
Appears in Collections:北京肿瘤医院

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