摘要
背景与目的:白藜芦醇具有广泛的抗肿瘤作用,其可抑制甲状腺乳头状癌细胞增殖和迁移,但是其发挥作用的相关机制尚不清楚。因此,本研究探讨白藜芦醇对甲状腺乳头状细胞癌移植瘤的抑制作用以及其作用机制。方法:将40只裸鼠背部皮下接种甲状腺乳头状癌细胞(TPC-1)悬液建立移植瘤模型后,随机分为模型对照组和3个不同剂量白藜芦醇(2.5、5、10 mg/kg)治疗组,每组10只。白藜芦醇各剂量组裸鼠分别腹腔注射相应剂量的白藜芦醇,模型对照组裸鼠腹腔注射等体积生理盐水,1次/d,连续21 d。记录移植瘤的生长情况,绘制生长曲线。21 d后处死各组小鼠,称量肿瘤质量,计算抑瘤率;行肿瘤组织HE染色和TUNEL染色检测肿瘤细胞形态和凋亡情况;用qRT-PCR法与Western blot法分别检测肿瘤组织中凋亡相关蛋白(caspase-3、Bax、Bcl-2)与上皮-间充质转化(EMT)相关分子(E-cadherin、N-cadherin、vimentin)的m RNA与蛋白表达。结果:与模型对照组比较,3个剂量白藜芦醇治疗组的移植瘤生长速度均被抑制,21 d后的移植瘤质量均明显减小,且抑瘤率随白藜芦醇剂量的增加而加大(均P<0.05)。HE染色结果显示,模型对照组肿瘤组织中癌细胞呈片状,形态大小不一,胞浆丰富,核大,可见核分裂象,极性紊乱;3个剂量白藜芦醇治疗组细胞数量均不同程度减少、细胞排列疏松、细胞核固缩、核分裂较少、不同程度片状坏死。与模型对照组比较,3个剂量白藜芦醇治疗组的肿瘤组织中肿瘤细胞凋亡增加;E-cadherin和Bax mRNA和蛋白表达量升高,N-cadherin、vimentin和Bcl-2 mRNA和蛋白表达量降低;caspase-3 mRNA水平降低,切割型caspase-3蛋白表达量升高,且以上变化在3个剂量白藜芦醇治疗组均呈剂量依赖性(均P<0.05)。结论:白藜芦醇可促进甲状腺癌细胞凋亡从而抑制其在小鼠体内的生长,其作用机制可能与逆转EMT过程有关。
Background and Aims:Resveratrol has a broad spectrum of anti-tumor effects,exhibiting the ability to inhibit proliferation and migration of papillary thyroid cancer cells.However,the underlying mechanisms of its actions remain unclear.This study was conducted to investigate the inhibitory effect of resveratrol on transplanted tumors of papillary thyroid cancer cells and its action mechanism.Methods:Forty nude mice were subcutaneously inoculated with thyroid cancer cells(TPC-1)to establish the xenograft models.Then,the tumor-bearing mice were randomly divided into a model control group and three resveratrol treatment groups receiving different doses of resveratrol(2.5,5,10 mg/kg),with each group containing 10 mice.Respective doses of resveratrol were administered by intraperitoneal injection to the mice in the treatment groups,while the model control group received an equivalent volume of physiological saline,once daily for 21 d.Tumor growth was monitored and growth curves were plotted.After 21 d,mice in each group were euthanized,tumors were weighed,and tumor inhibition rates were calculated.Histological examination with HE staining and TUNEL staining were performed to assess tumor cell morphology and apoptosis.qRT-PCR and Western blot analyses were used to evaluate the mRNA and protein expressions of apoptosis-related proteins(caspase-3,Bax,Bcl-2)and epithelial-mesenchymal transition(EMT)related molecules(E-cadherin,N-cadherin,vimentin)in tumor tissues.Results:In all three resveratrol treatment groups compared to the model control group,the growth rates of transplanted tumors were significantly inhibited,and after 21 d,tumor mass was noticeably reduced,and tumor inhibition rates increased with higher resveratrol doses(all P<0.05).Results of HE staining showed that in the model control group,cancer cells in the tumor tissue presented a patchy distribution with varied morphologies and sizes,rich cytoplasm,large nuclei,visible mitotic figures,and disrupted polarity.In contrast,in the resveratrol treatment groups wi
作者
毛姗
李扬
丁韩梦
赵永丽
MAO Shan;LI Yang;DING Hanmeng;ZHAO Yongli(Department of Pharmacy,Nanyang Medical College,Nanyang,Henan 473000,China;Pharmacy Department of Nanyang Zhang Zhongjing Hospital,Nanyang,Henan 473000,China)
出处
《中国普通外科杂志》
CAS
CSCD
北大核心
2023年第11期1770-1777,共8页
China Journal of General Surgery
基金
河南省医学科技攻关计划基金资助项目(LHGJ20200824)。
