Mifepristone inhibits non-small cell lung carcinoma cellular escape from DNA damaging cisplatin.
Mifepristone inhibits non-small cell lung carcinoma cellular escape from DNA damaging cisplatin.
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DOI：
10.1186/s12935-018-0683-z
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发表时间：
2018
影响因子：
5.8
通讯作者：
Telleria CM
中科院分区：
文献类型：
--
作者：
Kapperman HE;Goyeneche AA;Telleria CM
肺癌是世界上癌症死亡的主要原因。肺癌的主要组织病理学亚型是非小细胞肺癌（NSCLC）。含铂治疗是晚期NSCLC患者的标准治疗。然而，即使接受治疗，大多数患者也会在5年内死于这种疾病，其中大多数死亡是由于复发。抑制复发的一种策略是在致命化疗过程后使用细胞抑制化合物。我们已经在各种癌细胞类型中表明，米非司酮（MF），一种抗-β-肾上腺素/抗-糖皮质激素，是一种强大的细胞抑制性抗癌剂。因此，在这项工作中，我们测试的假设，MF应该是有效的诱导细胞抑制和预防复发的非小细胞肺癌顺铂（CDDP）治疗。我们建立了一种体外方法，其中将具有不同遗传背景和对CDDP敏感性的人NSCLC细胞（A549和H23）暴露于几轮致死浓度的CDDP 1小时，然后进行或不进行MF单药治疗。每2天，研究活细胞的细胞数量、细胞活力和集落形成能力。CDDP杀死了大多数细胞，但仍有残余细胞逃脱CDDP致死性并重新填充培养物，如活细胞的克隆形成存活率提高所证明的。相反，当暴露于CDDP的细胞在去除CDDP后进一步用MF处理时，它们的数量和克隆形成能力急剧降低。该研究报告了在致死浓度的CDDP单药治疗后NSCLC细胞的再增殖，NSCLC细胞对MF的生长抑制特性敏感，并且MF消除了CDDP治疗后NSCLC细胞的再增殖。我们的研究支持进一步评估MF作为NSCLC辅助治疗的价值。
Lung cancer is the leading cause of cancer deaths in the world. The major histopathological subtype of lung cancer is non-small cell lung cancer (NSCLC). Platinum-based therapy is the standard of care for patients with advanced stage NSCLC. However, even with treatment, most patients will die of this disease within 5 years and most of these deaths are due to recurrence. One strategy to inhibit recurrence is to use cytostatic compounds following courses of lethal chemotherapy. We have shown in various cancer cell types that mifepristone (MF), an anti-progestin/anti-glucocorticoid, is a powerful cytostatic anti-cancer agent. Thus, in this work we tested the hypothesis that MF should be efficacious in inducing cytostasis and preventing repopulation of NSCLC following cisplatin (CDDP) therapy. We established an in vitro approach wherein human NSCLC cells with different genetic backgrounds and sensitivities to CDDP (A549 and H23) were exposed to rounds of lethal concentrations of CDDP for 1 h followed or not by MF monotherapy. Every 2 days, cell number, cell viability, and colony-forming ability of viable cells were studied. CDDP killed the majority of cells, yet there were remnant cells escaping CDDP lethality and repopulating the culture, as evidenced by the improved clonogenic survival of viable cells. In contrast, when cells exposed to CDDP where further treated with MF following CDDP removal, their number and clonogenic capacity were reduced drastically. This study reports that there is repopulation of NSCLC cells following a lethal concentration of CDDP monotherapy, that NSCLC cells are sensitive to the growth inhibition properties of MF, and that MF abrogates the repopulation of NSCLC cells following CDDP therapy. Our study supports further evaluating MF as an adjuvant therapy for NSCLC.
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影响因子：
8
作者：
Cooke, S. L.;Ng, C. K. Y.;Melnyk, N.;Garcia, M. J.;Hardcastle, T.;Temple, J.;Langdon, S.;Huntsman, D.;Brenton, J. D.
通讯作者：
Brenton, J. D.
影响因子：
3.8
作者：
Brandhagen BN;Tieszen CR;Ulmer TM;Tracy MS;Goyeneche AA;Telleria CM
通讯作者：
Telleria CM
DOI：
10.1530/rep-14-0416
发表时间：
2015-01
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Goyeneche AA;Telleria CM
通讯作者：
Telleria CM
影响因子：
4.7
作者：
Coward J;Harding A
通讯作者：
Harding A
影响因子：
3.9
作者：
Erenpreisa, Jekaterina;Cragg, Mark S.
通讯作者：
Cragg, Mark S.