摘要
目的观察氟尿嘧啶缓释剂植入对子宫内膜癌裸鼠移植瘤生长的影响及其对非编码RNA母系表达基因3(LncRNA MEG3)和自噬的调控。方法用人子宫内膜癌RL-95-2细胞株建立裸鼠皮下移植瘤模型,分为三组:对照组不作处理;注射组通过尾静脉注射氟尿嘧啶(5-Fu),剂量为4 mg/kg;植入组瘤体内植入缓释剂,剂量为4 mg/kg。记录瘤体体积、瘤重,计算各组抑瘤率;HE染色观察瘤体形态学;qPCR和蛋白印迹分别检测基因和蛋白表达。结果与对照组相比,注射组和植入组瘤体体积和瘤体体重均减少(P<0.05);与注射组相比,植入组瘤体体积和瘤体体重均减少(P<0.05)。注射组抑瘤率为15.91%,植入组抑瘤率为34.47%。HE染色显示植入组坏死区域大于注射组。相对于对照组,注射组(t=3.328,P=0.0043)和植入组(t=5.367,P=0.0000)LC3-Ⅰ的表达降低,且植入组LC3-Ⅰ的表达低于注射组(t=2.400,P=0.0008),差异均有统计学意义。相对于对照组,注射组(t=4.178,P=0.0007)和植入组(t=6.764,P=0.0000)LC3-Ⅱ的表达升高,且植入组LC3-Ⅱ的表达高于注射组(t=2.683,P=0.0163),差异均有统计学意义。植入组瘤体LC3-Ⅱ/LC3-Ⅰ比值明显大于注射组,差异有统计学意义(t=5.571,P=0.0000)。注射组和植入组LncRNA MEG3和LC3-Ⅱ/LC3-Ⅰ比值呈正相关(r=0.8581、0.7135,P均<0.05)。结论氟尿嘧啶缓释剂对裸鼠子宫内膜癌的抑制效果好于静脉注射给药,其机制可能是通过LncRNA MEG3正性调控激活细胞自噬从而抑制肿瘤。
Objective To observe the effect of fluorouracil sustained release agent on endometrial carcinoma in nude mice and the regulation of LncRNA MEG3 and autophagy.Methods RL-95-2 cells were subcutaneous transplanted into nude mice to establish the colorectal carcinoma model,and divided it into 3 groups.The control group was not treated;the injection group was injected with 5-Fu via the tail vein at a dose of 4 mg/kg;the implantation group was implanted with a sustained-release agent in a dose of 4 mg/kg.Body weight,food intake,tumor volume and tumor weight were recorded.The tumors were harvested and conducted the H&E staining.The mRNA and protein expression were determined by qPCR and Western-blot,respectively.Results Compared with the control group,the tumor volume and tumor weight of the injection group and the implant group were decreased(P<0.05).Compared with the injection group,the tumor volume and tumor weight of the implant group were decreased(P<0.05).The inhibitory rate was 15.91%in the injection group and 34.47%in the implantation group.Compared with the control group,the LncRNA MEG3 expression was significantly increased in the injection group(t=6.652,P=0.0000)and the implanted group(t=10.08,P=0.0000),and the implantation group was greater than the injection group(t=4.105,P=0.0008).Compared with the control group,LC3-I expression was decreased in the injected group(t=3.328,P=0.0043)and the implanted group(t=5.367,P=0.0000),and the expression of LC3-I in the implanted group was lower than that of the injected group(t=2.400,P=0.0008).Compared with the control group,LC3-II expression was increased in the injected group(t=4.178,P=0.0007)and the implanted group(t=6.764,P=0.0000),and the expression of LC3-Ⅱin the implanted group was increased than that of the injected group(t=2.683,P=0.0163).The LC3-II/LC3-I ratio in the implanted group was significantly greater than that in the injection group(t=5.571,P=0.0000).There was a positive correlation between LncRNA MEG3 and LC3-II/LC3-I ratios in the injected group and in the implanted group(r=0.8581,0.7135,P<0.05).Conclusion Fluorouracil sustained-release was more effective than intravenous injection in inhibiting endometrial carcinoma in nude mice;the mechanism might be through the positive regulation of LncRNA MEG3 and activation of cell autophagy to inhibit tumors.
作者
赵艳华
邹小雪
ZHAO Yan hua;ZOU Xiao xue(Department of Gynecology,China Construction Third Engineering Bureau Co.,Ltd.Affiliated Wuhan Central Hospital,Wuhan,Hubei 430022,China)
出处
《热带医学杂志》
CAS
2019年第6期723-726,810,共5页
Journal of Tropical Medicine
