[1]姬国杰,丰慧根.大豆异黄酮协同索拉非尼对宫颈癌Hela细胞增殖、迁移的影响及机制[J].新乡医学院学报,2022,39(10):912-918.[doi:10.7683/xxyxyxb.2022.10.003]
　JI Guojie,FENG Huigen.Effect and mechanism of soybean isoflavones combined with sorafenib on proliferation and migration of cervical carcinoma Hela cells[J].Journal of Xinxiang Medical University,2022,39(10):912-918.[doi:10.7683/xxyxyxb.2022.10.003]
点击复制

大豆异黄酮协同索拉非尼对宫颈癌Hela细胞增殖、迁移的影响及机制
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年10
页码:
912-918
栏目:
基础研究
出版日期:
2022-10-05

文章信息/Info

Title:
Effect and mechanism of soybean isoflavones combined with sorafenib on proliferation and migration of cervical carcinoma Hela cells
作者:
姬国杰1; 2; 丰慧根1
（1.新乡医学院，河南　新乡　453003；2.新乡医学院三全学院生物与基础医学实验教学中心，河南　新乡　453000）
Author(s):
JI Guojie1; 2; FENG Huigen1
（1.Xinxiang Medical University,Xinxiang 453003,Henan Province,China;2.Experimental Teaching Center of Biology and Basic Medicine,Sanquan College of Xinxiang Medical University,Xinxiang 453000,Henan Province,China）
关键词:
Hela细胞; 血管内皮生长因子-C; 索拉非尼; 大豆异黄酮; 宫颈癌
Keywords:
Hela cells; vascular endothelial growth factor C; sorafenib; soybean isoflavones; cervical cancer
分类号:
Ｒ979.1
DOI:
10.7683/xxyxyxb.2022.10.003
文献标志码:
A
摘要:
目的　探讨大豆异黄酮协同索拉非尼对宫颈癌Hela细胞的增殖、迁移的影响及机制。方法　取对数生长期Hela细胞随机分为对照组、大豆异黄酮组、1 mmol·L-1索拉非尼组、2 mmol·L-1索拉非尼组、4 mmol·L-1索拉非尼组、6 mmol·L-1索拉非尼组、1 mmol·L-1索拉非尼+大豆异黄酮组、2 mmol·L-1索拉非尼+大豆异黄酮组、4 mmol·L-1索拉非尼+大豆异黄酮组、6 mmol·L-1索拉非尼+大豆异黄酮组，应用噻唑蓝法检测各组细胞增殖情况，划痕实验检测对照组、大豆异黄酮组、2 mmol·L-1索拉非尼组、2 mmol·L-1索拉非尼+大豆异黄酮组、4 mmol·L-1索拉非尼组、4 mmol·L-1索拉非尼+大豆异黄酮组细胞迁移情况，实时荧光定量-聚合酶链反应法检测对照组、大豆异黄酮组、4 mmol·L-1索拉非尼组、4 mmol·L-1索拉非尼+大豆异黄酮组细胞中血管内皮生长因子-C（VEGF-C） mRNA 相对表达量，Western blot法检测对照组、大豆异黄酮组、4 mmol·L-1索拉非尼组和4 mmol·L-1索拉非尼+大豆异黄酮组细胞中VEGF-C蛋白相对表达量。结果　1 mmol·L-1索拉非尼组、2 mmol·L-1索拉非尼组、4 mmol·L-1索拉非尼组、6 mmol·L-1索拉非尼组、1 mmol·L-1索拉非尼+大豆异黄酮组、2 mmol·L-1索拉非尼+大豆异黄酮组、4 mmol·L-1索拉非尼+大豆异黄酮组、6 mmol·L-1索拉非尼+大豆异黄酮组细胞增殖抑制率均高于对照组和大豆异黄酮组(P<0.05 )；大豆异黄酮组与对照组细胞增殖抑制率比较差异无统计学意义(P>0.05)；不同浓度索拉非尼组和不同浓度索拉非尼+大豆异黄酮组细胞增殖抑制率随索拉非尼浓度的增加呈增高趋势（P<0.05）；1 mmol·L-1索拉非尼组、2 mmol·L-1索拉非尼组、4 mmol·L-1索拉非尼组、6 mmol·L-1索拉非尼组细胞增殖抑制率分别高于对应的1 mmol·L-1索拉非尼+大豆异黄酮组、2 mmol·L-1索拉非尼+大豆异黄酮组、4 mmol·L-1索拉非尼+大豆异黄酮组、6 mmol·L-1索拉非尼+大豆异黄酮组 (P<0.05) 。2 mmol·L-1索拉非尼组、2 mmol·L-1索拉非尼+大豆异黄酮组、4 mmol·L-1索拉非尼组、4 mmol·L-1索拉非尼+大豆异黄酮组细胞迁移抑制率均显著高于对照组和大豆异黄酮组 (P<0.05 )；4 mmol·L-1索拉非尼组细胞迁移抑制率显著高于2 mmol·L-1索拉非尼组，4 mmol·L-1索拉非尼+大豆异黄酮组细胞迁移抑制率显著高于2 mmol·L-1索拉非尼+大豆异黄酮组（P<0.05）；2 mmol·L-1索拉非尼+大豆异黄酮组细胞迁移抑制率显著高于2 mmol·L-1索拉非尼组，4 mmol·L-1索拉非尼+大豆异黄酮组细胞迁移抑制率显著高于4 mmol·L-1索拉非尼组（P<0.05）。4 mmol·L-1索拉非尼组、4 mmol·L-1索拉非尼+大豆异黄酮组细胞VEGF-C mRNA和蛋白相对表达量均低于对照组和大豆异黄酮组（P<0.05）；对照组与大豆异黄酮组细胞中VEGF-C mRNA和蛋白相对表达量比较差异无统计学意义（P>0.05）；4 mmol·L-1索拉非尼+大豆异黄酮组细胞中VEGF-C mRNA和蛋白相对表达量低于4 mmol·L-1索拉非尼组（P<0.05）。结论　大豆异黄酮协同索拉非尼可通过降低VEGF-C基因和蛋白质表达抑制宫颈癌Hela细胞的增殖、迁移能力，且随索拉菲尼浓度升高抑制效果增强。
Abstract:
Objective　To investigate the effect of soybean isoflavones combined with sorafenib on the proliferation,migration of cervical carcinoma Hela cells and its mechanism.Methods　The Hela cells in logarithmic growth stage were randomly divided into control group,soybean isoflavones group,1 mmol·L－1 sorafenib group,2 mmol·L－1 sorafenib group,4 mmol·L－1 sorafenib group,6 mmol·L－1 sorafenib group,1 mmol·L－1 sorafenib+soybean isoflavones group,2 mmol·L－1 sorafenib+soybean isoflavones group,4 mmol·L－1 sorafenib+soybean isoflavones group,and 6 mmol·L－1 sorafenib+soybean isoflavones group,the cell proliferation in the each group was detected by Thiazole blue method,the cell migration in the control group,soybean isoflavones group,2 mmol·L－1 sorafenib group,2 mmol·L－1 sorafenib+ soybean isoflavones group,4 mmol·L－1 sorafenib group,4 mmol·L－1 sorafenib+soybean isoflavones group was detected by scratch test,the relative expression of vascular endothelial growth factor C (VEGF-C) mRNA in the cells in the control group,soybean isoflavones group,4 mmol·L－1 sorafenib group,4 mmol·L－1 sorafenib+soybean isoflavones group was detected by and fluorescence quantitative polymerase chain reaction,the relative expression of VEGF-C protein in the cells in the control group,soybean isoflavones group,4 mmol·L－1 sorafenib group and 4 mmol·L－1 sorafenib+soybean isoflavones group was detected by Western blot.Results　The cell proliferation inhibition rates in the 1 mmol·L-1 sorafenib group,2 mmol·L-1 sorafenib group,4 mmol·L-1 sorafenib group,6 mmol·L-1 sorafenib group,1 mmol·L-1 sorafenib+sorbean isoflavones group,2 mmol·L-1 sorafenib+sorbean isoflavones group,4 mmol·L-1 sorafenib+sorbean isoflavones group and 6 mmol·L-1 sorafenib+soybean isoflavones group were significantly higher than that in the control group and soybean isoflavones group(P<0.05);there was no significant difference in the cell proliforation inhibition rate between the soybean isoflavones group and control group.The cell proliferation inhibition rate in the different concentrations of sorafenib group and different concentrations of sorafenib+soybean isoflavones group significantly increased with the increase of concentration of sorafenib (P<0.05).The cell proliferation inhibition rates in the 1 mmol·L－1 sorafenib group,2 mmol·L－1 sorafenib group,4 mmol·L－1 sorafenib group and 6 mmol·L－1 sorafenib group were significantly higher than that in the 1 mmol·L－1 sorafenib+soybean isoflavones group,2 mmol·L－1 sorafenib+soybean isoflavones group,4 mmol·L－1 sorafenib+soybean isoflavones group and 6 mmol·L－1 sorafenib+soybean isoflavones group,respectively (P<0.05).The cell migration inhibition rate in the 2 mmol·L－1 sorafenib group,2 mmol·L－1 sorafenib+soybean isoflavones group,4 mmol·L－1 sorafenib group and 4 mmol·L－1 sorafenib+soybean isoflavones group were significantly higher than that in the control group and soybean isoflavones group (P<0.05);the cell migration inhibition rate in the 4 mmol·L－1 sorafenib group was significantly higher than that in the 2 mmol·L－1 sorafenib group (P<0.05),and the cell migration inhibition rate in the 4 mmol·L－1 sorafenib+soybean isoflavones group was significantly higher than that in the 2 mmol·L－1 sorafenib+soybean isoflavones group (P<0.05);the cell migration inhibition rate in the 2 mmol·L－1 sorafenib+soybean isoflavones group was significantly higher than that in the 2 mmol·L－1 sorafenib group,and the cell migration inhibition rate in the 4 mmol·L－1 sorafenib+soybean isoflavones group was significantly higher than that in the 4 mmol·L－1 sorafenib group (P<0.05).The relative expression of VEGF-C mRNA and protein in the 4 mmol·L－1 sorafenib group and the 4 mmol·L－1 sorafenib+soybean isoflavones group were significantly lower than those in the control group and soybean isoflavones group (P<0.05);there was no significant difference in the relative expression of VEGF-C mRNA and protein between the control group and the soybean isoflavones group (P>0.05);the relative expressions of VEGF-C mRNA and protein in the 4 mmol·L－1 sorafenib+soybean isoflavones group were significantly lower than that in the 4 mmol·L－1 sorafenib group (P< 0.05).Conclusion　Soybean isoflavones combined with sorafenib can inhibit the proliferation and migration of Hela cells by reducing the expression of VEGF-C gene and protein,and the inhibitory effect is enhanced with the increase of the concentration of sorafenib.

参考文献/References:

［1］　SIEGEL R L,MILLER K D,FUCHS H E,et al.Cancer statistics,2021［J］.CA Cancer J Clin,2021,71(1):7-33.
［2］　宗丽菊,向阳.晚期及复发宫颈癌免疫治疗的研究进展与未来［J］.中国实用妇科与产科杂志,2018,34(11):1211-1216.
ZONG L J,XIANG Y.Research progress and future of immunotherapy for advanced and recurrent cervical cancer［J］.Chin J Pract Gynecol Obstetr,2018,34(11):1211-1216.
［3］　董红玲.miR-543在宫颈癌中的表达及其对宫颈癌细胞侵袭与转移的影响［J］.现代肿瘤医学,2018,26(2):178-182.
DONG H L.The expression miR-543 in cervical cancer tissues and its effects on the migration and invasion of cervical cancer cells［J］.Modern Oncol,2018,26(2):178-182.
［4］　孟亚平.索拉非尼联合TACE治疗进展期原发性肝癌的临床研究［J］.肝脏,2016,21(10):867-870.
MENG Y P.Clinical study of sorafenib combined with TACE in the treatment of advanced primary liver cancer［J］.Chin Hepatol,2016,21 (10):867-870.
［5］　次旦旺久,林坤,卢再鸣,等.索拉菲尼抑制肿瘤细胞PKM2蛋白表达［J］.现代肿瘤医学,2019,27(22):3973-3976.
CIDAN W J,LIN K,LU Z M,et al.Experimental research about sorafenib inhibiting PKM2 protein expression in cancer cell line［J］.Modern Oncol,2019,27(22):3973-3976.
［6］　SIMENTAL-MENDA L E,GOTTO A M JR,ATKIN S L,et al.Effect of soy isoflavones supplementation on plasma lipoprotein(a) concentrations:a meta-analysis［J］.J Clin Lipidol,2018,12(1):16-24.
［7］　胡胜兰,肖昊,王丽,等.大豆异黄酮对体外氧化应激仔猪肠上皮细胞的影响及机制研究［J］.动物营养学报,2021,33(12):6699-6708.
HU S L H,XIAO H,WANG L,et al.Effects and mechanism research of soybean isoflavoness on intestinal epithelial cells of piglets under oxidative stress in vitro［J］.Chin J Animal Nutr,2021,33(12):6699-6708.
［8］　李雅萌,王亚茹,周柏松,等.异黄酮生物活性研究进展［J］.特产研究,2017,39(3):60-63.
LI Y M,WANG Y R,ZHOU B S,et al.Research progress on biological activity of isoflavones［J］.Special Wild Economic Animal Plant Res,2017,39(3):60-63.
［9］　YAMAGATA K.Soy isoflavoness inhibit endothelial cell dysfunction and prevent cardiovascular disease［J］.J Cardiovasc Pharmacol,2019,74(3):201-209.
［10］　邵晓洁,管文婕,洪占梅,等.大豆异黄酮通过NF-κB p65信号通路抑制Aβ1-42诱导的海马神经元炎症和凋亡［J］.中国药理学通报,2022,38(6):874-879.
SHAO X J,GUAN W J,HONG Z M,et al.Soy isoflavoness inhibit inflammation and apoptosis of hippocampal neurons induced by Aβ1-42 through NF-κB p65 signaling pathway［J］.Chin Pharmacolog Bull,2022,38(6):874-879.
［11］　胡焕焕,姬国杰,陈阳,等.不同剂量大豆苷元对宫颈癌细胞株Hela VEGF-C基因表达的影响［J］.山东医药,2018,58(3):36-38.
HU H H,JI G J,CHEN Y,et al.Effects of different doses of daidzein on the expression of VEGF-C gene in cervical cancer Hela cells［J］.Shandong Med J,2018,58(3):36-38.
［12］　王宇,宋淑芳,刘凤.我国宫颈癌流行病学特征和发病高危因素的研究进展［J］.中国妇幼保健,2019,34 (5):1206-1208.
WANG Y,SONG S F,LIU F.Research progress on epidemiological characteristics and high risk factors of cervical cancer in our country［J］.Matern Child Health Care China,2019,34(5):1206-1208.
［13］　张韶凯,赵方辉,乔友林.中国宫颈癌防治研究20年历程与成就［J］.中华流行病学杂志,2020,41(6):809-812.
ZHANG S K,ZHAO F H,QIAO Y L.Development and achievements regarding the prevention and control of cervical cancer in the last 20 years in China［J］.Chin J Epidemiol,2020,41(6):809-812.
［14］　KU M K,NT T T,HA M I,et al.Randomized,open label,multicenter,phase II trial of transcatheter arterial chemoembolization (TACE) therapy in combination with sorafenib as compared with TACE alone in patients with hepatocellular carcinoma:TACTICS trial［J］.J Clin Oncol,2018,36(15 suppl).
［15］　刘人杰.索拉菲尼治疗原发性肝癌的效果及对患者血清HSP90α、VEGF水平的影响［J］.中国医学创新,2021,18(14):15-19.
LIU R J.Effect of sorafenib in the treatment of primary liver cancer and its influence on serum HSP90α and VEGF levels［J］.Med Innov China,2021,18(14):15-19
［16］　OKUYAMA H,IKEDA M,KUWAHARA A,et al.Prognostic factors in patients with hepatocellular carcinoma refractory or intolerant to sorafenib［J］.Oncology,2015,88(4):241-246.
［17］　SONG C,ZHANG J,WEN R,et al.Improved anti-hepatocellular carcinoma effect by enhanced Co-delivery of Tim-3 siRNA and sorafenib via multiple pH triggered drug-eluting nanoparticles［J］.Mater Today Bio,2022,16:100350.
［18］　DUVAL A P,TROQUIER L,DE SOUZA SILVA O,et al.Diclofenac potentiates sorafenib-based treatments of hepatocellular carcinoma by enhancing oxidative stress［J］.Cancers (Basel),2019,11(10):1453.
［19］　ABDEL-RAHMAN O,FOUAD M.Sorafenib-based combination as a first line treatment for advanced hepatocellular carcinoma:a systematic review of the literature［J］.Crit Rev Oncol Hematol,2014,91(1):1-8.
［20］　CHRISTEN K E,DAVIS R A,KENNEDY D.Psammaplysin F increases the efficacy of bortezomib and sorafenib through regulation of stress granule formation［J］.Int J Biochem Cell Biol,2019,112:24-38.
［21］　GONG G,LIU Q,DENG Y,et al.Arabinogalactan derived from Lycium barbarum fruit inhibits cancer cell growth via cell cycle arrest and apoptosis［J］.Int J Biol Macromol,2020,149:639-650.
［22］　KIM I S.Current perspectives on the beneficial effects of soybean isoflavoness and their metabolites for humans［J］.Antioxidants (Basel),2021,10(7):1064.
［23］　HILLMAN G G.Soy isoflavoness protect normal tissues while enhancing radiation responses［J］.Semin Radiat Oncol,2019,29(1):62-71.
［24］　BROWNLOW B,NAGARAJ V J,NAYEL A,et al.Development and in vitro evaluation of vitamin E-enriched nanoemulsion vehicles loaded with genistein for chemoprevention against UVB-induced skin damage［J］.J Pharm Sci,2015,104(10):3510-3523.

相似文献/References:

[1]杨增周,席鸿钧,侯进荣.血管内皮生长因子-C及血管内皮生长因子受体-3在高发区食管鳞癌淋巴结转移中的作用[J].新乡医学院学报,2008,25(01):015.
[2]张雯珂１,武周炜２.青蒿琥酯对宫颈癌ＨｅＬａ细胞免疫抑制作用的影响[J].新乡医学院学报,2015,32(02):130.[doi:10.7683/xxyxyxb.2015.02.010]
[3]李　萍,姬白嫣,魏　娟,等.藏红花素对人宫颈癌Hela细胞顺铂耐药性的影响[J].新乡医学院学报,2021,38(5):401.[doi:10.7683/xxyxyxb.2021.05.001]
　LI Ping,JI Baiyan,WEI Juan,et al.Effect of crocin on cisplatin resistance of human cervical cancer Hela cells[J].Journal of Xinxiang Medical University,2021,38(10):401.[doi:10.7683/xxyxyxb.2021.05.001]

更新日期/Last Update: 2022-10-05