安石榴甙对骨肉瘤细胞增殖、迁移和侵袭的影响及其机制研究-东南大学学报医学版

安石榴甙对骨肉瘤细胞增殖、迁移和侵袭的影响及其机制研究

单位：海南省中医院肿瘤科, 海南海口 570203

分类号：R738

出版年·卷·期（页码）：2022·41·第二期（170-175）

摘要：

目的:探讨安石榴甙(PUN)对骨肉瘤(OS)细胞增殖、迁移和侵袭的影响及其可能机制。方法:选取OS的U2OS和MG63细胞,用不同浓度PUN处理,分别设置为不加PUN的对照组和50、75、100 μmol·L^-1 PUN组。用结晶紫法检测细胞增殖能力,细胞划痕愈合实验检测细胞迁移,Transwell小室法检测细胞侵袭和迁移,蛋白质印迹法检测分泌型糖蛋白/β-连锁蛋白通路相关蛋白(β-连环蛋白、c-Myc蛋白、细胞周期蛋白D1)和上皮间质转化(EMT)相关蛋白[E钙黏蛋白、N钙黏蛋白、波形纤维蛋白、锌指蛋白转录因子(ZEB1、Snial、Twist)]表达水平。结果:不同剂量PUN均可抑制U2OS和MG63细胞的增殖、侵袭和迁移,并且存在剂量依赖性,剂量越大,抑制作用越强(P＜0.05)。与对照组及50 μmol·L^-1组比较,75 μmol·L^-1及100 μmol·L^-1组N钙黏蛋白、波形纤维蛋白及ZEB1、Snial、Twist蛋白表达水平较低,而E钙黏蛋白表达水平较高(P＜0.05)。与对照组比较,75 μmol·L^-1组及100 μmol·L^-1组β-连环蛋白、c-Myc基因、细胞周期蛋白D1蛋白表达水平较低(P＜0.05)。结论:PUN可能通过抑制分泌型糖蛋白/β-连锁蛋白通路和EMT而抑制OS瘤细胞的增殖、侵袭、迁移。

Objective: To explore the effect of punica granaside(PUN) on the proliferation, migration and invasion of osteosarcoma(OS) cells and its possible mechanism. Methods: Osteosarcoma U2OS and MG63 cells were selected as the research objects. The two tumor cell lines were intervened with different concentrations of PUN(0, 50, 75, and 100 μmol·L^-1). Crystal violet method was employed to detect cell proliferation, cell scratch healing test was used to detect cell migration, and Transwell chamber method was used to detect cell invasion and migration. Western blot was used to determine Wnt/β-catenin pathway related proteins(β-catenin, c-Myc, Cyclin D1) and epithelial-mesenchymal transition(EMT) related proteins[E-cadherin, N-cadherin, vimentin, zinc finger protein transcription factors(ZEB1, Snial, Twist)] expression levels. Results: Different doses of PUN could inhibit the proliferation, invasion and migration of U2OS and MG63 cells with a dose-dependent manner. The higher the dose was, the stronger the inhibitory effect(P＜0.05). Compared with the control group and 50 μmol·L^-1 group, the N-cadherin, vimentin, ZEB1, Snial, and Twist protein expression levels were lower in the 75 μmol·L^-1 group and 100 μmol·L^-1 group, while the E-cadherin protein expression level was higher(P＜0.05). Compared with the control group, the expression levels of β-catenin, c-Myc and Cyclin D1 in the 75 μmol·L^-1 group and 100 μmol·L^-1 group were lower(P＜0.05). Conclusion: PUN inhibits the proliferation, invasion and migration of OS tumor cells by inhibiting the Wnt/β-catenin pathway and EMT.

参考文献：

[1] LILIENTHAL I,HEROLD N.Targeting molecular mechanisms underlying treatment efficacy and resistance in osteosarcoma:a review of current and future strategies[J].Int J Mol Sci,2020,21(18):6885.
[2] SAYLES L C,BREESE M R,KOEHNE A L,et al.Genome-informed targeted therapy for osteosarcoma[J].Cancer Discov,2019,9(1):46-63.
[3] 古丽米热,朱俊宇,梁华平,等.安石榴苷抗炎、抗氧化及抗感染活性的研究进展[J].感染、炎症、修复,2018,19(1):44-47.
[4] BERDOWSKA I,MATUSIEWICZ M,FECKA I.Punicalagin in cancer prevention-via signaling pathways targeting[J].Nutrients,2021,13(8):2733.
[5] GANESAN T,SINNIAH A,CHIK Z,et al.Punicalagin regulates apoptosis-autophagy switch via modulation of annexin a1 in colorectal cancer[J].Nutrients,2020,12(8):2430.
[6] YAO X,CHENG X,ZHANG L,et al.Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response[J].Nutr Res,2017,47:63-71.
[7] ZHANG Y,WANG X.Targeting the Wnt/β-catenin signaling pathway in cancer[J].J Hematol Oncol,2020,13(1):165.
[8] ZHU S,LIU Y,WANG X,et al.lncRNA SNHG10 promotes the proliferation and invasion of osteosarcoma via Wnt/β-catenin signaling[J].Mol Ther Nucleic Acids,2020,22:957-970.
[9] 吴晗,吴学建.免疫检查点分子B7-H3对骨肉瘤细胞增殖和转移的影响[J].中华实验外科杂志,2021,37(11):2039-2041.
[10] HARRISON D J,GELLER D S,GILL J D,et al.Current and future therapeutic approaches for osteosarcoma[J].Expert Rev Anticancer Ther,2018,18(1):39-50.
[11] CHEN C,XIE L,REN T,et al.Immunotherapy for osteosarcoma:fundamental mechanism,rationale,and recent breakthroughs[J].Cancer Lett,2021,500:1-10.
[12] LI G,XU Y,PAN L,et al.Punicalagin damages the membrane of salmonella typhimurium[J].J Food Prot,2020,83(12):2102-2106.
[13] 张宁,曹明浩,冶鹏辉,等.石榴皮多酚提取方法,活性及其应用研究进展[J].现代食品,2020,46(20):41-45,55.
[14] CHENG X,YAO X,XU S,et al.Punicalagin induces senescent growth arrest in human papillary thyroid carcinoma BCPAP cells via NF-κB signaling pathway[J].Biomed Pharmacother,2018,103:490-498.
[15] TANG J M,MIN J,LI B S,et al.Therapeutic effects of punicalagin against ovarian carcinoma cells in association with β-catenin signaling inhibition[J].Int J Gynecol Cancer,2016,26(9):1557-1563.
[16] ZHANG S,HE L,SHANG J,et al.Carvacrol suppresses human osteosarcoma cells via the Wnt/β-catenin signaling pathway[J].Anticancer Agents Med Chem,2021,34(12):113-119.
[17] CHEN T,CHEN Z,LIAN X,et al.MUC 15 promotes osteosarcoma cell proliferation,migration and invasion through livin,MMP-2/MMP-9 and Wnt/β-Catenin signal pathway[J].J Cancer,2021,12(2):467-473.
[18] LEI Y,CHEN L,ZHANG G,et al.MicroRNAs target the Wnt/β-catenin signaling pathway to regulate epithelial-mesenchymal transition in cancer(Review)[J].Oncol Rep,2020,44(4):1299-1313.
[19] WENG Z,PENG J,WU W,et al.Downregulation of PART1 inhibits proliferation and differentiation of hep3b cells by targeting hsa-miR-3529-3p/FOXC2 axis[J].J Oncol,2021,2021:7792223.
[20] ZHANG J,TEN DIJKE P,WUHRER M,et al.Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer[J].Protein Cell,2021,12(2):89-106.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录