Department of Acupuncture and Moxibustion, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518055, P.R. China.
Department of Clinical Laboratory, The People's Hospital of Longhua, Shenzhen, Guangdong 518109, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11881. Epub 2021 Feb 4.
Notoginsenoside R1 (NGR1), a monomer of Traditional Chinese medicine, is from the complex, and has been reported to inhibit the proliferation of various types of cancer. However the mechanism underlying NGR1‑mediated inhibition of cervical carcinoma cell proliferation remains unclear. Therefore, the current study aimed to investigate the antitumor effects of NGR1 on cervical carcinoma cell lines (CaSki and HeLa cells) . The Cell Counting Kit‑8 and soft agar cell colony formation assay results revealed that NGR1 suppressed the viability and the number colonies of CaSki and HeLa cells, respectively. Furthermore, the DAPI staining, flow cytometry and western blotting results revealed that NGR1 induced cervical carcinoma cell apoptosis, cell cycle arrest in the S phase, upregulation of cyclin A2 and CDK2 expression levels, and downregulation of cyclin D1 expression levels. To further investigate the mechanisms of NGR1, DNA‑damage‑related proteins, including H2A.X variant histone (H2AX), ATR serine/threonine kinase (ATR) and p53, and the nucleolus protein, plant homeodomain finger protein 6 (PHF6) were analyzed. The results indicated that NGR1 triggered the phosphorylation of H2AX and ATR in a dose‑ and time‑dependent manner, and downregulated the expression level of PHF6 and upregulated the expression level of p53 in a dose‑ and time‑dependent manner. In conclusion, the findings of the present indicated that NGR1 may inhibit the viability of cervical carcinoma cells and induce cell apoptosis via DNA damage, which may be activated by the downregulation of PHF6 expression levels, and the subsequent triggering of the phosphorylation of H2AX and ATR. In addition, NGR1 may exert an ability to arrest cervical carcinoma cells in the S phase and upregulate the expression levels of cyclin A2 and CDK2. Therefore, NGR1 may serve as a novel chemotherapeutic agent for cervical carcinoma.
三七总皂苷 R1（NGR1）是一种来自中药的单体，已被报道可抑制多种类型的癌症的增殖。然而，NGR1 介导的抑制宫颈癌细胞增殖的机制尚不清楚。因此，本研究旨在探讨 NGR1 对宫颈癌细胞系（CaSki 和 HeLa 细胞）的抗肿瘤作用。细胞计数试剂盒-8 和软琼脂细胞集落形成实验结果显示，NGR1 分别抑制了 CaSki 和 HeLa 细胞的活力和集落数。此外，DAPI 染色、流式细胞术和 Western blot 结果显示，NGR1 诱导宫颈癌细胞凋亡，细胞周期阻滞在 S 期，上调细胞周期蛋白 A2 和 CDK2 的表达水平，下调细胞周期蛋白 D1 的表达水平。为了进一步探讨 NGR1 的作用机制，分析了与 DNA 损伤相关的蛋白，包括 H2AX 变体组蛋白（H2AX）、ATR 丝氨酸/苏氨酸激酶（ATR）和 p53，以及核仁蛋白 PHF6。结果表明，NGR1 以剂量和时间依赖的方式触发 H2AX 和 ATR 的磷酸化，并以剂量和时间依赖的方式下调 PHF6 的表达水平，上调 p53 的表达水平。综上所述，本研究结果表明，NGR1 可能通过 DNA 损伤抑制宫颈癌细胞的活力并诱导细胞凋亡，这可能是通过下调 PHF6 的表达水平，继而触发 H2AX 和 ATR 的磷酸化而激活的。此外，NGR1 可能具有将宫颈癌细胞阻滞在 S 期并上调细胞周期蛋白 A2 和 CDK2 的表达水平的能力。因此，NGR1 可能作为一种新型的宫颈癌化疗药物。
