Department of Dermatology and Venereology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Cell Mol Med. 2024 Oct;28(19):e70122. doi: 10.1111/jcmm.70122.
Human papillomavirus (HPV) infection can cause condyloma acuminatum (CA), which is characterized by a high incidence and a propensity for recurrence after treatment. Angiogenesis plays an important role in the occurrence and development of CA. Seryl-tRNA synthetase (SerRS) is a newly identified, potent anti-angiogenic factor that directly binds to the vascular endothelial growth factor (VEGFA) promoter, thereby suppressing its transcription. Emodin is a natural anthraquinone derivative that can promote SerRS expression. This study aimed to investigate the effects of emodin on CA and explore combined treatment strategies. The HPV-infected cell line SiHa was treated with either DMSO, emodin, ALA-PDT or a combination of emodin and ALA-PDT. We observed the effects on cell proliferation, apoptosis and the SerRS-VEGFA pathway. Our findings demonstrated that emodin targets angiogenesis through the SerRS-VEGFA pathway, resulting in the inhibition of SiHa cell proliferation and promotion of apoptosis (p < 0.001). To verify the therapeutic effect of emodin combined with ALA-PDT on HPV-associated tumours in vivo, we established an animal xenograft model by subcutaneously inoculating mice with SiHa cells (n = 4). The results showed that the combination of emodin and ALA-PDT significantly inhibited the expression of VEGFA to inhibit angiogenesis (p < 0.001), thus showing an inhibitory effect on tumour (p < 0.001). Furthermore, we determined that the mechanism underlying the decrease in VEGFA expression after emodin combined with ALA-PDT in CA may be attributed to the promotion of SerRS expression (p < 0.001). The combination of emodin and ALA-PDT holds promise as a novel therapeutic target for CA by targeting neovascularization in condyloma tissues.
人乳头瘤病毒(HPV)感染可引起尖锐湿疣(CA),其特点是发病率高,治疗后易复发。血管生成在 CA 的发生和发展中起着重要作用。丝氨酰-tRNA 合成酶(SerRS)是一种新发现的强效抗血管生成因子,可直接与血管内皮生长因子(VEGFA)启动子结合,从而抑制其转录。大黄素是一种天然蒽醌衍生物,可促进 SerRS 的表达。本研究旨在探讨大黄素对 CA 的影响,并探索联合治疗策略。用 DMSO、大黄素、ALA-PDT 或大黄素和 ALA-PDT 联合处理 HPV 感染的细胞系 SiHa,观察对细胞增殖、凋亡和 SerRS-VEGFA 通路的影响。我们的研究结果表明,大黄素通过 SerRS-VEGFA 通路靶向血管生成,从而抑制 SiHa 细胞增殖并促进凋亡(p<0.001)。为了验证大黄素联合 ALA-PDT 对 HPV 相关肿瘤的体内治疗效果,我们通过皮下接种 SiHa 细胞建立了动物异种移植模型(n=4)。结果表明,大黄素联合 ALA-PDT 显著抑制 VEGFA 的表达,从而抑制血管生成(p<0.001),因此对肿瘤有抑制作用(p<0.001)。此外,我们确定大黄素联合 ALA-PDT 降低 CA 中 VEGFA 表达的机制可能归因于 SerRS 表达的促进(p<0.001)。大黄素联合 ALA-PDT 可能成为治疗 CA 的一种新的治疗靶点,通过靶向尖锐湿疣组织中的新生血管化。