Department of Biological Sciences, Faculty of Science, Beirut Arab University, P.O. Box 11-5020, Riad El Solh, Beirut 11072809, Lebanon.
Molecular Biology Unit, Department of Zoology, Faculty of Science, Alexandria University, Alexandria 21511, Egypt.
J Pharm Pharmacol. 2024 Jun 6;76(6):691-700. doi: 10.1093/jpp/rgae022.
Improving response rates in colorectal cancer (CRC) is an urgent clinical need. This study aimed to explore the synergistic action of Lebanese rosemary essential oil (REO) and 5-fluorouracil (5-FU) in HCT116 CRC cells.
We tested the cell viability of monotherapy and combination therapy. The combination index was calculated using CompuSyn software to evaluate drug-drug interactions and the level of synergistic cytotoxicity. We also evaluated cell migration and cytopathology. Furthermore, cell apoptosis-related proteins (i.e. Bax and Bcl-2) were measured by Western blot analysis.
The REO/5-FU combination synergistically reduced cell viability, effectively decreased cell migration, and increased the Bax/Bcl-2 ratio in HCT116 cells. This triggered a proapoptotic morphology and initiated an apoptotic cascade in HCT116 cells, as indicated by a higher Bax/Bcl-2 ratio.
Our results provide evidence of the REO/5-FU combination as a better approach to improve 5-FU anticancer efficacy and allow the use of lower 5-FU doses due to the adjuvant effect of REO.
提高结直肠癌(CRC)的反应率是一个迫切的临床需求。本研究旨在探索黎巴嫩迷迭香精油(REO)和 5-氟尿嘧啶(5-FU)在 HCT116 CRC 细胞中的协同作用。
我们测试了单药治疗和联合治疗的细胞活力。使用 CompuSyn 软件计算合并指数,以评估药物相互作用和协同细胞毒性的水平。我们还评估了细胞迁移和细胞病变。此外,通过 Western blot 分析测量细胞凋亡相关蛋白(即 Bax 和 Bcl-2)。
REO/5-FU 联合协同降低了 HCT116 细胞的活力,有效降低了细胞迁移,并增加了 Bax/Bcl-2 比值。这在 HCT116 细胞中引发了促凋亡形态,并启动了凋亡级联反应,Bax/Bcl-2 比值升高。
我们的研究结果为 REO/5-FU 联合作为提高 5-FU 抗癌疗效的更好方法提供了证据,并由于 REO 的辅助作用,可以使用较低剂量的 5-FU。