University of Sadat City (USC), Genetic Engineering and Biotechnology Research Institute (GEBRI), Department of Molecular Biology, PO Box 79 / 22857 Sadat City, Egypt.
An Acad Bras Cienc. 2022 Jul 22;94(2):e20200573. doi: 10.1590/0001-3765202120200573. eCollection 2022.
Telomerase is a ribonucleoprotein enzyme that plays a crucial role in maintaining the malignancy and is responsible for cellular immortality and tumorigenesis. On another hand, Centromere protein B (CENP-B) plays an important role in cell cycle regulation and helping in the high rate proliferation of cancer cells. Our study is designed to evaluate the effect of using combined antisense oligonucleotides (ASOs) targeting (hTR) and mRNA of CENP-B on liver cancer cells. Compared with a single treatment, combination treatment with Locked Nucleic Acid (LNA) ASO (hTR) and (CENP-B) (6.25 nM from each) exhibit the maximum synergistic cytotoxic effect. hTR and CENP-B mRNA was abrogated while hTERT expression was disappeared. Caspase-3, Bax, and Bcl-2 were not detected, indicating caspase-independent cell death. A significant reduction in [Tumor necrosis factor (TNF-α) and Transforming growth factor (TGF-β)] coincides with elevation in Nitric oxide (NO) secretions was observed. Taken together; our data suggest that combination treatment with LNA ASO (hTR) and (CENP-B) could provide a promising strategy for cancer treatment by controlling many pathways concurrently. This might open a new prospective application of antisense in cancer therapy.
端粒酶是一种核糖核蛋白酶，在维持恶性肿瘤中起着关键作用，负责细胞的永生和肿瘤发生。另一方面，着丝粒蛋白 B (CENP-B) 在细胞周期调控中起着重要作用，并有助于癌细胞的高增殖率。我们的研究旨在评估使用针对(hTR)和 CENP-B mRNA 的联合反义寡核苷酸 (ASO) 对肝癌细胞的影响。与单一治疗相比，使用锁定核酸 (LNA) ASO (hTR) 和 (CENP-B) (各 6.25 nM) 的联合治疗表现出最大的协同细胞毒性作用。hTR 和 CENP-B mRNA 被阻断，而 hTERT 表达消失。未检测到 caspase-3、Bax 和 Bcl-2，表明细胞死亡不依赖于 caspase。观察到肿瘤坏死因子 (TNF-α) 和转化生长因子 (TGF-β) 的显著减少与一氧化氮 (NO) 分泌的升高同时发生。总之，我们的数据表明，使用 LNA ASO (hTR) 和 (CENP-B) 的联合治疗可能通过同时控制多种途径为癌症治疗提供一种有前途的策略。这可能为癌症治疗中的反义技术开辟新的应用前景。
