Impact of H3K27 Demethylase Inhibitor GSKJ4 on NSCLC Cells Alone and in Combination with Metformin
Impact of H3K27 Demethylase Inhibitor GSKJ4 on NSCLC Cells Alone and in Combination with Metformin
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DOI：
10.21873/anticanres.11198
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发表时间：
2016-11-01
影响因子：
2
通讯作者：
Kitanaka, Chifumi
中科院分区：
文献类型：
--
作者：
Watarai, Hikaru;Okada, Masashi;Kitanaka, Chifumi
背景资料：据报道，GSKJ 4是一种H3 K27脱甲基酶抑制剂，对编码染色质调节剂的基因中含有遗传改变的特定癌症表现出抗肿瘤活性。然而，其作为抗癌剂对抗与这种遗传改变无关的人类癌症（包括非小细胞肺癌（NSCLC））的潜力仍然未知。材料与方法：使用WST-8、染料排除和集落形成试验研究了GSKJ 4对三种非小细胞肺癌细胞系和正常肺成纤维细胞生长的影响。结果如下：GSKJ 4单独使用或与抗糖尿病药物二甲双胍联合使用，在对正常细胞无毒的浓度下有效诱导细胞死亡并抑制NSCLC细胞系的生长，无论其遗传背景（KRAS、TP 53和EGFR基因突变）如何，也无论其对顺铂和紫杉醇的耐药性如何。结论：GSKJ 4是一种很有前途的非小细胞肺癌抗肿瘤药物，其抗肿瘤谱可能比以前认为的更广。
Background: GSKJ4, an H3K27 demethylase inhibitor, reportedly exhibits antitumor activity against specific cancers harboring genetic alterations in genes encoding chromatin modulators. However, its potential as an anticancer agent against human cancers not associated with such genetic alterations, including non-small cell lung cancer (NSCLC), remains unknown. Materials and Methods: The effect of GSKJ4 on the growth of three NSCLC cell lines and normal lung fibroblasts was investigated using the WST-8, dye exclusion, and colony formation assays. Results: GSKJ4, alone and in combination with an anti-diabetic drug metformin, induced cell death and inhibited the growth of NSCLC cell lines efficiently at concentrations non-toxic to normal cells, irrespective of their genetic backgrounds (mutations in the KRAS, TP53 and EGFR genes) and also of their resistance to cisplatin and paclitaxel. Conclusion: GSKJ4, being a promising anticancer agent for NSCLC, may be effective against a wider spectrum of cancers than previously thought.