摘要
目的基于PPARβ/Twist1信号通路,探讨委陵菜酸干预前列腺癌的作用及相关分子机制。方法体外培养人前列腺癌细胞株(LNCaP),加入不同浓度(10、20、40μmol/L)委陵菜酸进行干预。划痕实验和Transwell小室法分别检测细胞迁移、侵袭能力,Western blot检测细胞中PPARβ、Twist1、E-cadherin、N-cadherin、vimentin的表达情况。随后在BALB/c-nu裸鼠前列腺腺体背外侧包膜内注射LNCaP细胞悬液继而构建前列腺癌原位移植瘤模型,2周后灌胃不同浓度(0.75、1.5、3mg/kg)委陵菜酸进行治疗。取前列腺组织,测定药物治疗后瘤质量及瘤体积,HE染色法考察组织病理学改变,Western blot检测组织中PSA、PPARβ、Twist1、E-cadherin、N-cadherin、vimentin的表达情况。结果体外实验表明,委陵菜酸可有效抑制前列腺癌细胞迁移及浸润(P<0.01,P<0.05),WB检测结果显示:委陵菜酸可明显上调前列腺癌细胞中E-cadherin的表达水平(P<0.01,P<0.05),下调PPARβ、Twist1、N-cadherin及vimentin的表达水平(P<0.01,P<0.05)。体内实验表明,委陵菜酸可有效降低瘤质量及瘤体积(P<0.01,P<0.05)。结论委陵菜酸通过调控PPARβ/Twist1信号通路,抑制前列腺癌细胞的上皮细胞-间充质转化,从而有效发挥其抗前列腺癌迁移与侵袭的能力。
Objective Based on the PPAR Twist1 signaling pathway,to explore the effect and related molecular mechanism of tormentic acid on prostate cancer.Methods Human prostate cancer cell lines(LNCaP)were cultured in vitro,and different concentrations(10,20,40μmol/L)of tormentic acid were added for intervention.Cell migration and invasion ability were detected by the scratch experiment and the Transwell assay,respectively,and the expressions of PPARβ,Twist1,E-cadherin,N-cadherin and Vimentin were detected by western blot.Subsequently,LNCaP cell suspension was injected into the dorsal lateral capsule of prostate gland in BALB/c-nu nude mice,to construct an orthotopic transplanted tumor model of prostate cancer.Two weeks later,different concentrations(0.75,1.5,3mg/kg)of tormentic acid were treated by gavage.After drug treatment,prostate tissue was taken,and then tumor weight and tumor volume were measured.Results In vitro experiments showed that the tormentic acid could effectively inhibit prostate cancer cell migration and invasion(P<0.01,P<0.05).WB test results showed that tormentic acid could obviously increase E-cadherin expression levels in prostate cancer cells(P<0.01,P<0.05),decreased PPARβ,Twist1,N-cadherin and Vimentin expression levels(P<0.01,P<0.05).In vivo experiments showed that tormentic acid could effectively reduce tumor weight and tumor volume(P<0.01,P<0.05).Conclusion Tormentic acid can inhibit epithelial-mesenchymal transformation of prostate cancer cells by regulating PPARβ/Twist1 signaling pathway,so as to play an effective role in preventing migration and invasion of prostate cancer cells.
出处
《浙江临床医学》
2020年第6期771-773,共3页
Zhejiang Clinical Medical Journal
基金
浙江省自然科学基金资助项目(LQ20H050001)
温州市科技计划项目(Y20180481)。
