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通过小干扰RNA介导下调DLGAP1-AS2表达提高肺癌细胞对卡铂的化疗敏感性

Improvement of carboplatin chemosensitivity in lung cancer cells by siRNA-mediated downregulation of DLGAP1-AS2 expression.

作者信息

Alamdari Sania Ghobadi, Mohammadzadeh Reza, Amini Mohammad, Najafi Souzan, Baradaran Behzad, Bahojb Mahdavi Seyedeh Zahra, Yari Amirhossein, Mokhtarzadeh Amir Ali

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Cell and Molecular Biology, Faculty of Basic Science, University of Maragheh, Maragheh, Iran.

出版信息

Sci Rep. 2025 Mar 7;15(1):7971. doi: 10.1038/s41598-025-87649-6.

Abstract

Despite being one of the primary and most effective treatments for advanced stages of lung cancer, chemotherapy drugs like carboplatin have limitations due to their adverse side effects and the development of drug resistance in lung cancer cells. However, recent studies have shown promising results in using small interfering RNAs (siRNAs) as a therapeutic agent for cancer treatment. Hence, this study aimed to investigate the potential of combining siRNA-DLGAP1-AS2 with carboplatin in human lung cancer cell lines. The viability of the cells was assessed using the MTT assay, and apoptosis induction was examined through Annexin V/Pi staining. Additionally, the effect of the combination on cell cycle arrest and colony formation of lung cancer cells was studied. Furthermore, the expression of Bax, Bcl-2, MMP-2, MMP-9, GCLC, and CD44 was evaluated. Our functional analysis revealed that inhibiting the expression of DLGAP1-AS2 increased the sensitivity of lung cancer cells to carboplatin. Moreover, our study demonstrated that the combination of DLGAP1-AS2 inhibition through siRNA-DLGAP1-AS2 transfection and carboplatin treatment had a tumor-suppressive function, inhibiting the progression and proliferation of A549 lung cancer cells. Therefore, it can be concluded that targeting DLGAP1-AS2 using specific siRNA in combination with carboplatin chemotherapy holds promise as a valuable therapeutic approach for lung cancer.

摘要

尽管作为肺癌晚期主要且最有效的治疗方法之一,像卡铂这样的化疗药物因其副作用以及肺癌细胞中耐药性的产生而存在局限性。然而,最近的研究表明,使用小干扰RNA(siRNA)作为癌症治疗的治疗剂取得了有前景的结果。因此,本研究旨在探讨在人肺癌细胞系中将siRNA-DLGAP1-AS2与卡铂联合使用的潜力。使用MTT法评估细胞活力,并通过Annexin V/Pi染色检测细胞凋亡诱导情况。此外,研究了该联合用药对肺癌细胞周期阻滞和集落形成的影响。此外,还评估了Bax、Bcl-2、MMP-2、MMP-9、GCLC和CD44的表达。我们的功能分析表明,抑制DLGAP1-AS2的表达可增加肺癌细胞对卡铂的敏感性。此外,我们的研究表明,通过siRNA-DLGAP1-AS2转染抑制DLGAP1-AS2与卡铂治疗的联合具有肿瘤抑制功能,可抑制A549肺癌细胞的进展和增殖。因此,可以得出结论,使用特异性siRNA靶向DLGAP1-AS2并联合卡铂化疗有望成为一种有价值的肺癌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b965/11889186/77e59b73374e/41598_2025_87649_Fig1_HTML.jpg

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