A combination of valproic acid sodium salt, CHIR99021, E-616452, tranylcypromine, and 3-Deazaneplanocin A causes stem cell-like characteristics in cancer cells.
A combination of valproic acid sodium salt, CHIR99021, E-616452, tranylcypromine, and 3-Deazaneplanocin A causes stem cell-like characteristics in cancer cells.
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丙戊酸钠盐、CHIR99021、E-616452、反苯环丙胺和 3-Deazaneplanocin A 的组合可在癌细胞中产生干细胞样特征
DOI：
10.18632/oncotarget.18396
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发表时间：
2017-08-08
期刊：
影响因子：
--
通讯作者：
Liu G
中科院分区：
文献类型：
--
作者：
Sha S;Zhai Y;Lin C;Wang H;Chang Q;Song S;Ren M;Liu G
许多研究都基于这样的假设，即肺癌的复发和耐药是由于实体瘤中的癌症干细胞样细胞（CSLC）亚群。因此，筛查和识别肺CSLC至关重要。在这项研究中，我们使用五种小分子化合物的组合刺激非小细胞肺癌（NSCLC）A549细胞以显示干细胞样特征。推定的A549干细胞激活了一种重要的CSLC标志物CD 133蛋白，以及多种CSLC相关基因，包括ATP结合盒转运蛋白G2（ABCG 2）、C-X-C趋化因子受体4型（CXCR 4）、NESTIN和BMI 1。A549干细胞样细胞表现出对化疗药物依托泊苷和顺铂的抗性，上皮向间质转化的特性，以及NOTCH 1和Hes家族bHLH转录因子1（HES 1）蛋白表达水平的增加。当A549细胞在化合物诱导前用NOTCH信号通路抑制剂预处理时，NOTCH 1靶基因HES 1的表达降低。这表明推定的A549干细胞样细胞中的NOTCH信号通路已被激活。总之，我们的研究结果表明，五种小分子药物的组合可以将A549细胞转化为假定的干细胞样细胞，并且这些化合物还可以提高H460细胞中的CD 133和ABCG 2蛋白表达水平。本研究提供了一种简便的获得肺CSLCs的方法，这可能是开发肺癌治疗的有效策略。
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1. The A549 stem-like cells displayed resistance to the chemotherapeutic drugs etoposide and cisplatin, epithelial-to-mesenchymal transition properties, and increased protein expression levels of NOTCH1 and Hes Family bHLH Transcription Factor 1 (HES1). When A549 cells were pretreated with a NOTCH signaling pathway inhibitor before compound induction, expression of the NOTCH1 target gene HES1 was reduced. This demonstrated that the NOTCH signaling pathway in the putative A549 stem-like cells had been activated. Together, the results of our study showed that a combination of five small molecule agents could transform A549 cells into putative stem-like cells, and that these compounds could also elevate CD133 and ABCG2 protein expression levels in H460 cells. This study provides a convenient method for obtaining lung CSLCs, which may be an effective strategy for developing lung carcinoma treatments.
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DOI：
10.1074/jbc.m114.548651
发表时间：
2014-03-21
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fujiwara T;Saitoh H;Inoue A;Kobayashi M;Okitsu Y;Katsuoka Y;Fukuhara N;Onishi Y;Ishizawa K;Ichinohasama R;Harigae H
通讯作者：
Harigae H
DOI：
10.1111/resp.12094
发表时间：
2013-07
期刊：
Respirology (Carlton, Vic.)
影响因子：
--
作者：
Alamgeer M;Peacock CD;Matsui W;Ganju V;Watkins DN
通讯作者：
Watkins DN
影响因子：
3.7
作者：
Levina V;Marrangoni AM;DeMarco R;Gorelik E;Lokshin AE
通讯作者：
Lokshin AE
影响因子：
23.9
作者：
Ichida JK;Blanchard J;Lam K;Son EY;Chung JE;Egli D;Loh KM;Carter AC;Di Giorgio FP;Koszka K;Huangfu D;Akutsu H;Liu DR;Rubin LL;Eggan K
通讯作者：
Eggan K
影响因子：
5.8
作者：
Greenblatt, David Yu;Vaccaro, Abram M.;Chen, Herbert
通讯作者：
Chen, Herbert