摘要
目的探究瑞马唑仑(Rem)对宫颈癌裸鼠肿瘤生长、微血管生成和Wnt/β-catenin通路的影响。方法构建宫颈癌裸鼠模型共30只,分为空白对照组、模型组、低剂量组、中剂量组、高剂量组、高剂量+SKL2001组(Wnt/β-catenin激活剂),每组各5只。分别采用无任何处理、0 mg/kg Rem、5 mg/kg Rem、10 mg/kg Rem、20 mg/kg Rem、20 mg/kg Rem+10mg/kg SKL2001治疗空白对照组、模型组、低剂量组、中剂量组、高剂量组、高剂量+SKL2001组宫颈癌裸鼠。分析各组裸鼠肿瘤质量、体积差异,采用TUNEL实验检测各组裸鼠肿瘤组织细胞凋亡水平,通过Western blot检测各组裸鼠肿瘤组织MMP2、MMP9、VEGF、Wnt1、Wnt3a、β-catenin、NLRP3、N-GSDMD蛋白表达水平,采用免疫组织化学染色法检测各组裸鼠肿瘤组织微血管密度。结果与模型组裸鼠相比,低剂量组、中剂量组、高剂量组、高剂量+SKL2001组裸鼠肿瘤质量、体积和微血管密度均显著减少,肿瘤细胞凋亡数量增加,肿瘤组织MMP2、MMP9、VEGF、Wnt1、Wnt3a、β-catenin表达水平均显著降低,而NLRP3、N-GSDMD蛋白水平显著升高。与高剂量组裸鼠相比,高剂量+SKL2001组裸鼠肿瘤质量、体积和微血管密度有所增加,肿瘤细胞凋亡数量有所减少,肿瘤组织MMP2、MMP9、VEGF、Wnt1、Wnt3a、β-catenin表达水平均有所增加,NLRP3、N-GSDMD蛋白水平有所降低。结论Rem通过降低Wnt/β-catenin通路的表达来抑制宫颈癌裸鼠肿瘤生长和微血管生成,并诱导肿瘤细胞焦亡和凋亡。
Objective To investigate the effects of remimazolam(Rem)on tumor growth,angiogenesis,and the Wnt/β-catenin pathway in nude mice with cervical cancer.Methods A total of 25 nude mice models of cervical cancer were established and divided into model group,low-dose group,medium-dose group,high-dose group,high-dose+SKL2001 group(Wnt/β-catenin activator),with 5 nude mice in each group.The nude mice of cervical cancer in the model group,low-dose group,medium-dose group,high-dose group,and high-dose+SKL2001 group were treated with 0 mg/kg Rem,5 mg/kg Rem,10 mg/kg Rem,20 mg/kg Rem,20 mg/kg Rem+10 mg/kg SKL2001,respectively.The tumor mass and volume differences of each group of nude mice were analyzed,and the apoptosis level of tumor tissue cells in each group of nude mice was detected by TUNEL experiment.The protein expression levels of MMP2,MMP9,VEGF,Wnt1,Wnt3a,β-catenin,NLRP3,and N-GSDMD in tumor tissues of each group of nude mice were detected by Western blot.The microvessel density of tumor tissues in each group of nude mice was detected by immunohistochemical staining.Results Compared with the model group nude mice,the tumor weight,volume and microvessel density of the low-dose group,medium-dose group,high-dose group and high-dose+SKL2001 group nude mice were significantly reduced,and the expression levels of MMP2,MMP9,VEGF,Wnt1,Wnt3a,andβ-catenin in tumor tissues were significantly decreased,while the protein levels of NLRP3,N-GSDMD were significantly increased.Compared with the high-dose group nude mice,the tumor weight,volume and microvessel density of the high-dose+SKL2001 group nude mice were increased,and the expression levels of MMP2,MMP9,VEGF,Wnt1,Wnt3a,andβ-catenin in tumor tissues were increased,and the protein levels of NLRP3,N-GSDMD were decreased.Conclusion Rem suppressed the growth of cervical cancer xenografts and microvessel generation in nude mice and induced pyroptosis of tumor cells by downregulating the expression of the Wnt/β-catenin pathway.
作者
陈小芳
梁宏
杨婧
CHEN Xiaofang;LIANG Hong;YANG Jing(Department of Anesthesiology,Guangyuan Hospital of Traditional Chinese Medicine,Guangyuan,Sichuan 628000,China)
出处
《中国优生与遗传杂志》
2025年第9期1913-1918,共6页
Chinese Journal of Birth Health & Heredity
基金
2023年四川省医学重点学科(实验室、专科)、卫生健康科研课题、卫生适宜技术推广项目(23PJ164)。
