Department of Otolaryngology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, P. R. China.
Department of Traditional Chinese Medicine, Hi-tech Zhonghe Community Health Service Center, Chengdu, P. R. China.
Cancer Gene Ther. 2022 Jul;29(7):973-983. doi: 10.1038/s41417-021-00385-7. Epub 2021 Nov 9.
Dysregulation of the cell cycle and the resulting aberrant cellular proliferation has been highlighted as a hallmark of cancer. Certain traditional Chinese medicines can inhibit cancer growth by inducing cell cycle arrest. In this study we explore the effect of Hedyotis diffusae Herba-Andrographis Herba on the cell cycle of nasopharyngeal carcinoma (NPC). Hedyotis diffusae Herba-Andrographis Herba-containing serum was prepared and then added to the cell culture medium. BrdU, comet, and FUCCI assays, western blot analysis and flow cytometry analysis revealed that Hedyotis diffusae Herba-Andrographis Herba treatment significantly alters cell proliferation, DNA damage, and cell cycle distribution. Xenograft mouse model experiments were performed, confirming these in vitro findings in vivo. Treatment with Hedyotis diffusae Herba-Andrographis Herba inhibited cell proliferation, promoted DNA damage, and arrested NPC cells progression from G1 to S phase. Further examination of the underlying molecular mechanisms revealed that treatment with Hedyotis diffusae Herba-Andrographis Herba increased the expression of p53 and p21, while reducing that of CCND1, Phospho-Rb, E2F1, γH2AX, and Ki-67 both in vivo and in vitro. Conversely, the inhibition of p53 and p21 could abolish the promoting effect of Hedyotis diffusae Herba-Andrographis Herba on the NPC cell cycle arrest at the G1 phase, contributing to the proliferation of NPC cells. Hedyotis diffusae Herba-Andrographis Herba suppressed the tumor growth in vivo. Overall, these findings suggest that Hedyotis Diffusae Herba-Andrographis prevent the progression of NPC by inducing NPC cell cycle arrest at the G1 phase through a p53/p21-dependent mechanism, providing a novel potential therapeutic treatment against NPC.
细胞周期失调和由此导致的异常细胞增殖已被强调为癌症的一个标志。某些中药可以通过诱导细胞周期停滞来抑制肿瘤生长。在这项研究中,我们探讨了白花蛇舌草和穿心莲对鼻咽癌(NPC)细胞周期的影响。制备含白花蛇舌草和穿心莲的血清,然后加入细胞培养液中。BrdU、彗星和 FUCCI 检测、Western blot 分析和流式细胞术分析表明,白花蛇舌草和穿心莲处理显著改变细胞增殖、DNA 损伤和细胞周期分布。进行了异种移植小鼠模型实验,体内验证了这些体外发现。白花蛇舌草和穿心莲处理抑制细胞增殖,促进 DNA 损伤,并使 NPC 细胞从 G1 期停滞在 S 期。进一步研究潜在的分子机制表明,白花蛇舌草和穿心莲处理增加了 p53 和 p21 的表达,同时降低了 CCND1、磷酸化-Rb、E2F1、γH2AX 和 Ki-67 的表达,无论是在体内还是在体外。相反,抑制 p53 和 p21 可以消除白花蛇舌草和穿心莲对 NPC 细胞 G1 期周期阻滞的促进作用,促进 NPC 细胞的增殖。白花蛇舌草和穿心莲在体内抑制肿瘤生长。总的来说,这些发现表明,白花蛇舌草和穿心莲通过一种依赖 p53/p21 的机制诱导 NPC 细胞周期停滞在 G1 期,从而阻止 NPC 的进展,为 NPC 提供了一种新的潜在治疗方法。