Department of Biochemistry, School of Pharmacy, Newgiza University (NGU), Newgiza, Km 22 Cairo-Alexandria Desert Road, 6th of October, P.O. Box 12577, Giza, Egypt.
School of Pharmacy, Newgiza University (NGU), Newgiza, Km 22 Cairo-Alexandria Desert Road, P.O. Box 12577, Giza, Egypt.
Sci Rep. 2024 Jan 22;14(1):1844. doi: 10.1038/s41598-024-51977-w.
Tamoxifen (TAM) is one of the most successful treatments for breast cancer; however, TAM resistance continues to be a significant barrier. TAM resistance has been reported to be associated with increased expression of human telomerase reverse transcriptase (hTERT). This enzyme shares structural similarity with RNA-dependent RNA polymerase (RdRp) enzyme of RNA viruses, suggesting that RdRp inhibitors may also inhibit hTERT. Favipiravir (FAV) is an antiviral drug that inhibits RdRp of RNA viruses. Thus, we propose that FAV may also elicit an antitumor effect by suppressing hTERT. This study aimed to investigate the effect of FAV and TAM on TAM-resistant breast cancer (TAMR-1). The cell viabilities were determined. The levels of CDK1/ hTERT, in addition to regulators of hTERT-targeted signaling pathways were measured. Apoptosis, migration, and cell cycle distribution were also determined. Our data revealed that the combination of TAM and FAV suppressed cell proliferation synergistically (CI < 1) and resulted in a significant change in cell migration and apoptosis. Indeed, this was associated with reduced levels of hTERT and CDK1 and shift in the cell cycle distribution. Our findings suggest that the TAM/FAV combination exhibits synergistic effects against TAMR-1 human breast cancer cells by targeting hTERT.
他莫昔芬（TAM）是治疗乳腺癌最成功的方法之一；然而，TAM 耐药性仍然是一个重大障碍。据报道，TAM 耐药性与人类端粒酶逆转录酶（hTERT）的表达增加有关。这种酶与 RNA 病毒的 RNA 依赖性 RNA 聚合酶（RdRp）酶具有结构相似性，这表明 RdRp 抑制剂也可能抑制 hTERT。法匹拉韦（FAV）是一种抑制 RNA 病毒 RdRp 的抗病毒药物。因此，我们提出 FAV 也可能通过抑制 hTERT 发挥抗肿瘤作用。本研究旨在探讨 FAV 和 TAM 对 TAM 耐药性乳腺癌（TAMR-1）的影响。测定细胞活力。测定 CDK1/hTERT 水平，以及 hTERT 靶向信号通路的调节剂。还测定了细胞凋亡、迁移和细胞周期分布。我们的数据显示，TAM 和 FAV 的联合使用具有协同抑制细胞增殖的作用（CI<1），并导致细胞迁移和凋亡发生显著变化。事实上，这与 hTERT 和 CDK1 水平降低以及细胞周期分布的改变有关。我们的研究结果表明，TAM/FAV 联合用药通过靶向 hTERT 对 TAMR-1 人乳腺癌细胞表现出协同作用。
