Oral and Maxillofacial Department of Pathology, Faculty of Dentistry, Urmia Medical University, Urmia, West Azerbaijan, Iran.
Oral and Maxillofacial Department of Pathology, Faculty of Dentistry, Tabriz Medical University, Tabriz, East Azerbaijan, Iran.
Gene. 2019 Sep 25;714:143997. doi: 10.1016/j.gene.2019.143997. Epub 2019 Jul 23.
Based on Akt1 and Jak1 key roles in apoptosis and proliferation of many cancers, the aim of this study was to find a new gene therapy strategy by silencing of these main anti-apoptotic genes for HNSCC treatment. Cancerous HN5 and normal HUVEC cell lines were treated with Akt1 and Jak1 siRNAs alone or with each other combined with/without cisplatin. The MTS, flow cytometry, 4',6-diamidino-2-phenylindole staining, real-time PCR and ELISA methods were utilized in this study. The highest percentage of apoptosis was observed in the treatment of Jak1 siRNA/cisplatin group in cancerous HN5 cells (96.5%) where this treatment showed 12.84% apoptosis in normal HUVEC cell line. Cell viability reduced significantly to 64.57% after treatment with Akt1 siRNA in HN5 treated group. Knocking down Akt1 and Jak1 genes using siRNAs could increase levels of apoptosis and reduce proliferation rate in HNSCC indicating the powerful effects of these genes siRNAs with or without chemotherapeutic agents in HNSCC treatment. In conclusion, the combination of siRNA-mediated gene-silencing strategy can be considered as a valuable and safe approach for sensitizing cancer cells to chemotherapeutic agents thus proposed further studies regarding this issue to approve some siRNA based therapeutics for using in clinic.
基于 Akt1 和 Jak1 在许多癌症的凋亡和增殖中的关键作用，本研究旨在通过沉默这些主要抗凋亡基因来寻找新的基因治疗策略，以治疗头颈部鳞状细胞癌（HNSCC）。用 Akt1 和 Jak1 siRNA 单独或联合并用/不用顺铂处理癌性 HN5 和正常 HUVEC 细胞系。本研究中使用了 MTS、流式细胞术、4'，6-二脒基-2-苯基吲哚染色、实时 PCR 和 ELISA 方法。在癌性 HN5 细胞中，Jak1 siRNA/顺铂组观察到的凋亡率最高（96.5%），而在正常 HUVEC 细胞系中，这种治疗方法显示出 12.84%的凋亡率。在用 Akt1 siRNA 处理 HN5 组后，细胞活力显著降低至 64.57%。用 siRNA 敲低 Akt1 和 Jak1 基因可增加 HNSCC 中的细胞凋亡水平并降低增殖率，表明这些基因 siRNA 在有无化疗药物的情况下对头颈部鳞状细胞癌治疗具有强大的作用。总之，siRNA 介导的基因沉默策略的组合可被认为是使癌细胞对化疗药物敏感的有价值且安全的方法，因此建议进一步研究该问题，以批准一些基于 siRNA 的疗法用于临床。
