Abstract
背景与目的肺癌是危害身体健康的常见恶性肿瘤之一。随着表观遗传学的发展，研究者发现Zeste基因增强子同源物基因2（enhancer of Zeste homolog 2, EZH2）在肺癌中高表达且其表达量与预后息息相关，与此同时EZH2抑制剂也被发现能够提升肿瘤细胞对多种抗肿瘤药物的敏感性。本研究的目的在于探讨EZH2抑制剂与吉非替尼（gefitinib）联合应用，对耐吉非替尼细胞的增殖、凋亡及迁移的影响。方法以PC9吉非替尼敏感细胞和PC9/AB2吉非替尼耐药细胞为研究对象，应用CCK-8及EdU实验检测联合用药对于细胞活性及增殖的影响；通过划痕及Transwell小室检测联合用药对于细胞迁移能力的影响；并应用流式细胞学检测联合用药对于细胞凋亡的影响；并通过Western blot观察联合用药对EZH2及表皮生长因子（epidermal growth factor receptor, EGFR）信号通路相关蛋白的作用。结果在吉非替尼耐药细胞PC9/AB2细胞中，联合EZH2抑制剂GSK343与吉非替尼能够显著抑制耐药细胞的活性，降低细胞的迁移能力并诱导耐药细胞的凋亡。同时，联合用药也能够显著抑制EZH2表达及EGFR蛋白的磷酸化。结论EZH2抑制剂GSK343与吉非替尼联合应用能够克服PC9/AB2对吉非替尼的耐药作用，此研究也提示协同治疗在肺癌EGFR-TKIs耐药逆转中具有一定的作用。
Published Version
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