EGFR甲基化对肺腺癌细胞裸鼠移植瘤生长的影响

Effect of EGFR methylation on the growth of lung adenocarcinoma xenograft in nude mice

目的 探讨EGFR启动子甲基化对肺腺癌细胞裸鼠移植瘤生长的影响,为解决肺腺癌细胞对EGFR-TKIs耐药提供新的方法。方法 采用甲基化转移酶抑制剂5-氮杂-2’-脱氧胞苷(5-aza-CdR)及吉非替尼(一代EGFR-TKI),分别及联合处理肺腺癌细胞株H1299(原发耐药)、H1975(T790M突变,继发耐药)、HCC827(19外显子敏感突变)。进一步将三株细胞建成裸鼠移植瘤模型,观察在裸鼠体内5-aza-CdR是否可以提高肺腺癌细胞对吉非替尼的敏感性。结果 通过裸鼠移植瘤试验证实在活体内5-aza-CdR联合吉非替尼可以提高继发性耐药细胞株H1975对吉非替尼的敏感性。结论 EGFR启动子高甲基化可能参与了肺腺癌细胞对吉非替尼的继发性耐药。5-aza-CdR联合吉非替尼可以部分改善肺腺癌细胞对吉非替尼的继发性耐药。

Objective To investigate the effect of EGFR promoter methylation on the growth of lung adenocarcinoma xenograft in nude mice.Methods Lung adenocarcinoma cell lines H1299(primary drug resistance),H1975(T790M mutation,secondary drug resistance)and HCC827(exon 19 sensitive mutation)were treated with methyltransferase inhibitor 5-aza-2'-deoxycytidine(5-aza-CdR)and gefitinib(first-generation EGFR-TKI),respectively and in combination.The three cell lines were further established into a nude mouse xenograft model to observe whether 5-aza-CdR can increase the sensitivity of lung adenocarcinoma cells to gefitinib in nude mice.Results In vivo,5-aza-CdR combined with gefitinib could increase the sensitivity of secondary resistant cell line H1975 to gefitinib in nude mice.Conclusion EGFR promoter hypermethylation may be involved in the secondary resistance of lung adenocarcinoma cells to gefitinib.Combination of 5-aza-CdR and gefitinib improved the secondary resistance of lung adenocarcinoma cells to gefitinib.