姜黄素与 5-氟尿嘧啶联合应用对三阴性乳腺癌细胞抗癌活性的协同作用。
Synergistic Role of Thymoquinone on Anticancer Activity of 5-Fluorouracil in Triple Negative Breast Cancer Cells.
机构信息
Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China.
Advanced Bioinformatics, Computational Biology and Data Science Laboratory, Bangladesh, Chattogram, Bangladesh.
出版信息
Anticancer Agents Med Chem. 2022;22(6):1111-1118. doi: 10.2174/1871520621666210624111613.
BACKGROUND
Triple Negative Breast Cancer (TNBC) is considered as the most deadly subtype of breast cancer, because of heterogeneity, less treatment options and resistance to chemotherapy.
OBJECTIVE
To find out an efficient chemotherapeutic options, in this study we have investigated the combined therapy of 5-Fluorouracil (5-FU) and thymoquinone (TQ) against TNBC cell lines BT-549 and MDA-MB-231.
METHODS
We have tested 5-FU and TQ alone and in combination (5-FU + TQ) to observe the cellular growth, cell cycle and apoptosis status of BT-549 and MDA-MB-231 cells. Also we have measured the mRNA level expression of genes related to cell cycle and apoptosis.
RESULTS
Experimental results suggest that both of 5-FU and TQ are effective in controlling cell growth, cell cycle and inducing apoptosis, but their combination is much more effective. 5-FU was found to be more effective in controlling cell growth, while TQ was found to be more effective in inducing apoptosis, but in both cases, their combination was most effective. TQ was found more effective in increasing and BAX/BCL-2 ratio, while 5-FU was more effective in inhibiting thymidylate synthase. They showed significant increasing effects on caspases and P53 and decreasing effect on CDK-2, where their combination was found most effective.
CONCLUSION
Thus, TQ and 5-FU probably showed synergistic effect on both of cell cycle and apoptosis of tested TNBC cell lines. Our study reveals that TQ can synergise 5-FU action, and increase its anticancer efficiency against TNBC cells, which might be good choice in drug development for TNBC treatment.
背景
三阴性乳腺癌（TNBC）被认为是最致命的乳腺癌亚型，因为其异质性、治疗选择较少以及对化疗的耐药性。
目的
为了寻找有效的化疗选择，本研究探讨了 5-氟尿嘧啶（5-FU）和姜黄素（TQ）联合治疗 TNBC 细胞系 BT-549 和 MDA-MB-231 的效果。
方法
我们单独和联合测试了 5-FU 和 TQ（5-FU+TQ），以观察 BT-549 和 MDA-MB-231 细胞的细胞生长、细胞周期和凋亡状态。我们还测量了与细胞周期和凋亡相关的基因的 mRNA 水平表达。
结果
实验结果表明，5-FU 和 TQ 单独使用都能有效控制细胞生长、细胞周期和诱导凋亡，但两者联合使用效果更显著。5-FU 在控制细胞生长方面更有效，而 TQ 在诱导凋亡方面更有效，但在两种情况下，联合使用效果最显著。TQ 更有效地增加和 BAX/BCL-2 比值，而 5-FU 更有效地抑制胸苷酸合成酶。它们对 Caspases 和 P53 有显著的上调作用，对 CDK-2 有下调作用，联合使用效果最显著。
结论
因此，TQ 和 5-FU 可能对所测试的 TNBC 细胞系的细胞周期和凋亡具有协同作用。我们的研究表明，TQ 可以协同 5-FU 的作用，提高其对 TNBC 细胞的抗癌效率，这可能是开发 TNBC 治疗药物的一个不错选择。
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