Department of Gynecology, Shaanxi Provincial People's Hospital, Xi'an , 710068, Shaanxi, China.
Eur J Med Res. 2024 Sep 11;29(1):456. doi: 10.1186/s40001-024-02050-9.
Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.
卵巢癌是一种极其恶性的妇科肿瘤，患者预后较差，常伴有化疗耐药。因此，探索提高肿瘤化疗敏感性的新治疗方法很重要。据报道，转录延伸因子 B 多肽 2（TCEB2）基因在获得性耐药的卵巢癌肿瘤组织中表达上调，但肿瘤耐药的具体机制尚不清楚。在本研究中，我们发现 TCEB2 在顺铂耐药肿瘤组织和细胞中异常高表达。沉默 TCEB2 还抑制了 SKOV-3/顺铂（DDP）和 A2780/DDP 细胞的生长和糖酵解。我们进一步用敲低 TCEB2 的顺铂耐药细胞的培养上清液孵育人脐静脉内皮细胞（HUVEC）。结果表明，HUVEC 的迁移、侵袭和血管生成明显受到抑制。在线生物信息学分析显示，缺氧诱导因子-1A（HIF-1A）蛋白可能与 TCEB2 结合，沉默 TCEB2 通过下调 HIF1A 表达抑制 SKOV-3/DDP 细胞的生长和糖酵解。同样，TCEB2 通过上调 HIF1A 表达促进 HUVEC 的迁移、侵袭和血管生成。体内实验表明，沉默 TCEB2 增强了卵巢癌裸鼠对顺铂的敏感性，而敲低 TCEB2 抑制了肿瘤细胞的糖酵解和血管生成。我们的研究结果可为治疗化疗耐药的卵巢癌提供参考。
