Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Bioengineered. 2021 Dec;12(1):1505-1516. doi: 10.1080/21655979.2021.1916271.
As a common muscle relaxant, cisatracurium has shown good antitumor effect on some tumors. Recent studies reported that cisatracurium could inhibit the progression of colon cancer by upregulating tumor suppressor gene p53. However, its role in ovarian cancer and its regulatory effect on p53 and p53 downstream targeting gene long intergenic noncoding RNA p21 (lincRNA-p21) is still unknown. Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to assess the expression of p53, lincRNA-p21 and miR-181b. Cell viability and proliferation were detected by CCK-8 assay and Edu staining, respectively. Wound-healing and Transwell assays were performed to determine the abilities of cell migration and invasion. Apoptosis was evaluated by TUNEL staining. Luciferase reporter assay was conducted to detect the relationship between lincRNA-p21 and miR-181b. As a result, cisatracurium could increase the expressions of p53 and lincRNA-p21 of ovarian cancer cell line (OVCAR-3) in a dose-dependent manner. In addition, cisatracurium significantly inhibited the proliferation, migration and invasion of OVACR-3 cells, and induced apoptosis. However, these above changes in biological function can be attenuated by lincRNA-p21 knockdown. Next, lincRNA-p21 could directly target miR-181b and negatively regulate its expression by luciferase reporter assay. In conclusion, cisatracurium inhibited the progression of OVCAR-3 cells through upregulation of lincRNA-p21 expression activated by p53 inhibiting miR-181b expression. The experimental results provide a new research idea for the application of cisatracurium in ovarian cancer.
作为一种常用的肌肉松弛剂,顺式阿曲库铵已显示出对某些肿瘤的良好抗肿瘤作用。最近的研究报道,顺式阿曲库铵通过上调抑癌基因 p53 抑制结肠癌的进展。然而,它在卵巢癌中的作用及其对 p53 和 p53 下游靶基因长链非编码 RNA p21(lincRNA-p21)的调节作用尚不清楚。采用实时定量聚合酶链反应(qRT-PCR)检测 p53、lincRNA-p21 和 miR-181b 的表达。通过 CCK-8 检测和 Edu 染色分别检测细胞活力和增殖。采用划痕愈合和 Transwell 实验检测细胞迁移和侵袭能力。通过 TUNEL 染色评估细胞凋亡。通过荧光素酶报告实验检测 lincRNA-p21 和 miR-181b 之间的关系。结果表明,顺式阿曲库铵可呈剂量依赖性增加卵巢癌细胞系(OVCAR-3)中 p53 和 lincRNA-p21 的表达。此外,顺式阿曲库铵显著抑制 OVACR-3 细胞的增殖、迁移和侵袭,并诱导细胞凋亡。然而,通过 lincRNA-p21 敲低可减弱这些生物学功能的变化。接下来,通过荧光素酶报告实验证实 lincRNA-p21 可直接靶向 miR-181b,并负调控其表达。总之,顺式阿曲库铵通过 p53 激活上调 lincRNA-p21 表达抑制 miR-181b 表达来抑制 OVCAR-3 细胞的进展。实验结果为顺式阿曲库铵在卵巢癌中的应用提供了新的研究思路。