Advances in Understanding How RhoB Regulates Akt Inhibition Efficacy in NSCLC.

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2025-01-16 DOI:10.2174/0115680096355061241115113703

Nurullah Akgun, Zekai Halici, Elif Cadirci

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引用次数: 0

Abstract

Objectives: Increasing the effectiveness and reliability of Akt inhibition in lung cancer treatment may pave the way for a more favorable use of this method in the future. Therefore, we aimed to evaluate the possible role of RhoB in the regulation of Akt inhibition in NSCLC.

Material and methods: The study was conducted using the NSCLC cell line A549. Small interfering RNA (siRNA)-mediated RhoB knockdown was performed and combined with perifosine (Akt inhibitor) treatment. Cell proliferation was detected by xCELLigence® RTCA. RhoB, pAkt, and Bcl2l11 expressions were analyzed by ELISA. Apoptosis rates were determined by flow cytometry.

Results: We knocked down RhoB in A549 cells using siRNA. According to the results of the 72-hour experiment, RhoB upregulation was observed to reduce the antiproliferative ac-tivity of the Akt inhibitor. The pAkt level was significantly lower in the group where the Akt inhibitor was applied to RhoB-silenced cells via siRNA compared to other treatment groups. The percentage of apoptosis in the group where the Akt inhibitor was applied to RhoB-silenced cells was found to be significantly higher than in the RhoB-suppressed group.

Conclusion: Both proliferation and apoptosis tests determined that the RhoB molecule is a negative regulator of the anti-tumor activity of Akt inhibition in non-small cell lung cancer. This study suggests that RhoB expression may play a critical role in the regulation of Akt inhibition in NSCLC, potentially opening new avenues for treatment strategies.

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RhoB调控非小细胞肺癌中Akt抑制作用的研究进展

目的：提高Akt抑制在肺癌治疗中的有效性和可靠性，可能为该方法在未来的更有利应用铺平道路。因此，我们旨在评估RhoB在非小细胞肺癌中调控Akt抑制的可能作用。材料和方法：本研究采用非小细胞肺癌细胞系A549进行。小干扰RNA （siRNA）介导的RhoB敲低并联合perifosine （Akt抑制剂）治疗。xCELLigence®RTCA检测细胞增殖。ELISA检测RhoB、pAkt、bcl2111的表达。流式细胞术检测细胞凋亡率。结果：利用siRNA敲除A549细胞中的RhoB。根据72小时实验结果，RhoB上调可降低Akt抑制剂的抗增殖活性。与其他治疗组相比，Akt抑制剂通过siRNA作用于rhob沉默细胞组的pAkt水平显著降低。Akt抑制剂作用于rhob沉默细胞组的细胞凋亡百分比明显高于rhob抑制组。结论：在非小细胞肺癌中，增殖和凋亡实验均表明RhoB分子是Akt抑制的负调控因子。本研究提示RhoB表达可能在非小细胞肺癌的Akt抑制调控中发挥关键作用，可能为治疗策略开辟新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.