PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells.
PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells.
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DOI：
10.3390/ijms22116131
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发表时间：
2021-06-07
影响因子：
5.6
通讯作者：
Hamid Q
中科院分区：
文献类型：
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作者：
Bajbouj K;Ramakrishnan RK;Saber-Ayad M;Omar HA;Saheb Sharif-Askari N;Shafarin J;Elmoselhi AB;Ihmaid A;AlHaj Ali S;Alalool A;Abdullah R;Hamid Q
作为一种治疗方法，表观遗传修饰剂具有增强化疗药物疗效的潜力。蛋白质精氨酸甲基转移酶5（PRMT 5）在肺腺癌中高表达，被认为与肿瘤的发生有关。在目前的研究中，我们检测了PRMT 5抑制剂、精氨酸甲基转移酶抑制剂1（AMI-1）和顺铂对肺腺癌的潜在抑制活性。生物信息学分析确定细胞凋亡、DNA损伤和细胞周期进展为PRMT 5相关的主要功能途径，生存分析将PRMT 5基因表达增加与肺腺癌总体生存率降低联系起来。AMI-1和顺铂联合治疗显著降低细胞活力并诱导细胞凋亡。A549和DMS 53细胞在AMI-1后细胞周期阻滞明显，并且在联合处理后得到加强。蛋白质印迹分析显示，在单独使用AMI-1或与顺铂联合治疗后，PRMT 5下游靶点去甲基化组蛋白4减少。虽然组合方法解决了肺癌细胞存活问题，但它对HBEpC（正常上皮细胞）表现出细胞保护能力。正常支气管上皮细胞的存活不受AMI-1的影响。这项研究突出了AMI-1与顺铂联合在肺腺癌细胞中的新的选择性抗肿瘤活性的证据。
As a therapeutic approach, epigenetic modifiers have the potential to enhance the efficacy of chemotherapeutic agents. Protein arginine methyltransferase 5 (PRMT5), highly expressed in lung adenocarcinoma, was identified to be involved in tumorigenesis. In the current study, we examined the potential antineoplastic activity of PRMT5 inhibitor, arginine methyltransferase inhibitor 1 (AMI-1), and cisplatin on lung adenocarcinoma. Bioinformatic analyses identified apoptosis, DNA damage, and cell cycle progression as the main PRMT5-associated functional pathways, and survival analysis linked the increased PRMT5 gene expression to worse overall survival in lung adenocarcinoma. Combined AMI-1 and cisplatin treatment significantly reduced cell viability and induced apoptosis. Cell cycle arrest in A549 and DMS 53 cells was evident after AMI-1, and was reinforced after combination treatment. Western blot analysis showed a reduction in demethylation histone 4, a PRMT5- downstream target, after treatment with AMI-1 alone or in combination with cisplatin. While the combination approach tackled lung cancer cell survival, it exhibited cytoprotective abilities on HBEpC (normal epithelial cells). The survival of normal bronchial epithelial cells was not affected by using AMI-1. This study highlights evidence of novel selective antitumor activity of AMI-1 in combination with cisplatin in lung adenocarcinoma cells.
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DOI：
10.1042/bj20120768
发表时间：
2012-09-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Gu Z;Gao S;Zhang F;Wang Z;Ma W;Davis RE;Wang Z
通讯作者：
Wang Z
影响因子：
3.7
作者：
Kong GM;Yu M;Gu Z;Chen Z;Xu RM;O'Bryant D;Wang Z
通讯作者：
Wang Z
影响因子：
6.6
作者：
Lee, Sangchul;Yoon, Cheol Yong;Lee, Sang Eun
通讯作者：
Lee, Sang Eun
影响因子：
9.7
作者：
Jing, Pengyu;Zhao, Nan;Gu, Zhongping
通讯作者：
Gu, Zhongping
影响因子：
9
作者：
通讯作者：
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