Department of Pharmacology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang.
Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
Anticancer Drugs. 2023 Aug 1;34(7):803-815. doi: 10.1097/CAD.0000000000001475. Epub 2022 Dec 19.
The triple-negative breast cancer (TNBC) subtype is the most aggressive type of breast cancer with a low survival prognosis and high recurrence rate. There is currently no effective treatment to improve it. In this work, we explored the effect of a synthetic compound named WXJ-103 on several aspects of TNBC biology. The human breast cancer cell lines MDA-MB-231 and MCF-7 were used in the experiments, and the cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, and the cell migration and invasion abilities were detected by wound healing assay and Transwell invasion assay. Cell cycle and apoptosis experiments were analyzed by flow cytometry, and protein levels related to cyclin-dependent kinase (CDK) 4/6-cyclin D-Rb-E2F pathway were analyzed by western blotting. Then, in-vivo experiments were performed to determine the clinical significance and functional role of WXJ-103. The results show that WXJ-103 can inhibit the adhesion, proliferation, migration, and invasion of TNBC cells, and can arrest the cell cycle in G1 phase. The levels of CDK4/6-cyclin D-Rb-E2F pathway-related proteins such as CDK6 and pRb decreased in a dose-dependent manner. Therefore, the antitumor activity of WXJ-103 may depend on the inhibition of CDK4/6-cyclin D1-Rb-E2F pathway. This research shows that WXJ-103 may be a new promising antitumor drug, which can play an antitumor effect on TNBC and provide new ideas for the treatment of TNBC.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌类型，预后不良且复发率高。目前尚无有效的治疗方法来改善它。在这项工作中，我们探索了一种名为 WXJ-103 的合成化合物对 TNBC 生物学几个方面的影响。实验中使用了人乳腺癌细胞系 MDA-MB-231 和 MCF-7，通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法检测细胞活力，通过划痕愈合试验和 Transwell 侵袭试验检测细胞迁移和侵袭能力。通过流式细胞术分析细胞周期和凋亡实验，通过 Western blot 分析与细胞周期蛋白依赖性激酶（CDK）4/6-细胞周期蛋白 D-Rb-E2F 通路相关的蛋白水平。然后，进行体内实验以确定 WXJ-103 的临床意义和功能作用。结果表明，WXJ-103 可以抑制 TNBC 细胞的黏附、增殖、迁移和侵袭，并且可以将细胞周期阻滞在 G1 期。CDK4/6-细胞周期蛋白 D-Rb-E2F 通路相关蛋白如 CDK6 和 pRb 的水平呈剂量依赖性降低。因此，WXJ-103 的抗肿瘤活性可能依赖于对 CDK4/6-细胞周期蛋白 D1-Rb-E2F 通路的抑制。这项研究表明，WXJ-103 可能是一种有前途的新型抗肿瘤药物，对 TNBC 具有抗肿瘤作用，并为 TNBC 的治疗提供了新的思路。
