The Effect of Knockdown TIGAR on Apoptotic and Epithelial‐Mesenchymal Markers Expression in Doxorubicin‐Resistant Non‐Small Cell Lung Cancer A549 Cell Line,Chemistry & Biodiversity

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The Effect of Knockdown TIGAR on Apoptotic and Epithelial‐Mesenchymal Markers Expression in Doxorubicin‐Resistant Non‐Small Cell Lung Cancer A549 Cell Line
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2020-09-03 , DOI: 10.1002/cbdv.202000441
Can Ali Agca ₁ , Mahinur Kırıcı ₂ , Victor S Nedzvetsky _{1,

3} , Ramazan Gundogdu ₄ , Artem A Tykhomyrov ₅

Affiliation

Resistance to chemotherapeutic drugs is a critical problem in cancer therapy, but the underlying mechanism has not been fully elucidated. TP53‐induced glycolysis regulatory phosphatase (TIGAR), an important glycolysis and apoptosis regulator, plays a crucial role in cancer cell survival by protecting cells against oxidative stress‐induced apoptosis. In the present study, we investigated whether TIGAR is involved in epithelial‐mesenchymal transition (EMT) in doxorubicin (DOX)‐resistant human non‐small cell lung cancer (NSCLC), A549/DOX cells. We found that the expression of TIGAR was significantly higher in A549/DOX cells than in the parent A549 cell lines. siRNA‐mediated TIGAR knockdown reduced migration, viability and colony survival of doxorubicin‐resistant lung cancer cells. Also, TIGAR knockdown decreased pro‐survival protein Bcl‐2 and increased pro‐apoptotic Bax and cleaved poly (ADP‐ribose) polymerase (PARP). Moreover, TIGAR depletion significantly up‐regulated both caspase‐3 and caspase‐9 expression. Furthermore, TIGAR depletion up‐regulated the expression of E‐cadherin and down‐regulated the expression of vimentin. These results indicate that TIGAR knockdown may inhibit EMT in doxorubicin (DOX)‐resistant human NSCLC and may represent a therapeutic target for a non‐small lung cancer cells chemoresistance.

中文翻译：

敲低 TIGAR 对多柔比星抗性非小细胞肺癌 A549 细胞系凋亡和上皮间充质标志物表达的影响

对化疗药物的耐药性是癌症治疗中的一个关键问题，但其潜在机制尚未完全阐明。TP53 诱导的糖酵解调节磷酸酶 (TIGAR) 是一种重要的糖酵解和细胞凋亡调节剂，通过保护细胞免受氧化应激诱导的细胞凋亡，在癌细胞存活中起着至关重要的作用。在本研究中，我们调查了 TIGAR 是否参与阿霉素 (DOX) 耐药的人类非小细胞肺癌 (NSCLC) A549/DOX 细胞的上皮间质转化 (EMT)。我们发现 TIGAR 在 A549/DOX 细胞中的表达明显高于亲本 A549 细胞系。siRNA 介导的 TIGAR 敲低降低了耐多柔比星肺癌细胞的迁移、活力和集落存活。还，TIGAR 敲低降低了促存活蛋白 Bcl-2，增加了促凋亡 Bax 和裂解的聚（ADP-核糖）聚合酶（PARP）。此外，TIGAR 消耗显着上调 caspase-3 和 caspase-9 的表达。此外，TIGAR 耗竭上调 E-cadherin 的表达并下调波形蛋白的表达。这些结果表明，TIGAR 敲低可能会抑制多柔比星 (DOX) 耐药的人类 NSCLC 中的 EMT，并可能代表非小肺癌细胞化学耐药性的治疗靶点。

更新日期：2020-09-03

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