Targeted therapy for cancer stem-like cells of non-small cell lung cancers with inhibition of the cJun transcription factor

在非小细胞肺癌(NSCLC)细胞中，cJun抑制可降低无血清培养条件下肿瘤干细胞的成球能力，而在SCID小鼠中，成球细胞并未表现出增强的致瘤性。同时，通过表观遗传调节参与干细胞维持的组蛋白甲基转移酶抑制剂EZH2抑制了NSCLC细胞的生长。另一种表观遗传调节因子组蛋白脱乙酰酶(HDAC)的抑制剂与EZH2抑制剂显示出协同抑制生长的作用。联合使用EZH2抑制剂和HDAC抑制剂进行表观遗传治疗可能是治疗非小细胞肺癌的有效方法。

Sphere forming capacity under serum-free culture, indicative of cancer stem cells, were decreased by cJun inhibition in non-small lung cancer (NSCLC) cells, while sphere forming cells did not show enhanced tumorigenicity in SCID mice.Meanwhile, an inhibitor of histone methyltransferase EZH2 involved in stem cell maintenance via epigenetic regulation suppressed growth of NSCLC cells. An inhibitor of histone deacetylase (HDAC), another epigenetic regulator, showed a synergistic growth suppressive effect with the EZH2 inhibitor. Combined epigenetic therapy with an EZH2 inhibitor and an HDAC inhibitor may represent an effective approach for NSCLCs.