白花蛇舌草和半枝莲乙醇提取物逆转耐阿霉素肝细胞癌的耐药机制研究

潘云翠; 王倩; 胡爱艳; 徐怡; 聂笑宇; 张鑫; 王守梅; 张树辉

doi:10.16305/j.1007-1334.2021.2101014

您当前的位置：

首页 >

文章列表页 >

白花蛇舌草和半枝莲乙醇提取物逆转耐阿霉素肝细胞癌的耐药机制研究

实验研究 | 更新时间：2022-08-03

- 白花蛇舌草和半枝莲乙醇提取物逆转耐阿霉素肝细胞癌的耐药机制研究
- Mechanism of reversal of adriamycin-resistant hepatocellular carcinoma with ethanol extracts of Oldenlandia diffusa roxb and Scutellariae barbatae herba
- 上海中医药杂志 2021年55卷第10期页码：52-57
- 作者机构：
  
  1.上海中医药大学附属岳阳中西医结合医院病理科（上海　200437）
- 作者简介：
  
  潘云翠，女，博士研究生，主要从事中医药防治肝癌的研究工作
  张树辉，主任医师，博士研究生导师；E-mail：shzhang@126.com
- 基金信息：
  
  国家自然科学基金项目(81172311);上海中医药大学中西医高原学科项目(30304114325)
- DOI：10.16305/j.1007-1334.2021.2101014
  中图分类号：
扫描看全文
潘云翠, 王倩, 胡爱艳, 等. 白花蛇舌草和半枝莲乙醇提取物逆转耐阿霉素肝细胞癌的耐药机制研究[J]. 上海中医药杂志, 2021,55(10):52-57.

Yuncui PAN, Qian WANG, Aiyan HU, et al. Mechanism of reversal of adriamycin-resistant hepatocellular carcinoma with ethanol extracts of Oldenlandia diffusa roxb and Scutellariae barbatae herba[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(10):52-57.
潘云翠, 王倩, 胡爱艳, 等. 白花蛇舌草和半枝莲乙醇提取物逆转耐阿霉素肝细胞癌的耐药机制研究[J]. 上海中医药杂志, 2021,55(10):52-57. DOI： 10.16305/j.1007-1334.2021.2101014.

Yuncui PAN, Qian WANG, Aiyan HU, et al. Mechanism of reversal of adriamycin-resistant hepatocellular carcinoma with ethanol extracts of Oldenlandia diffusa roxb and Scutellariae barbatae herba[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(10):52-57. DOI： 10.16305/j.1007-1334.2021.2101014.

摘要

目的,2,研究白花蛇舌草（Od）和半枝莲（Sb）乙醇提取物对耐阿霉素肝细胞癌（HepG2/ADM）增殖和凋亡的作用。,方法,2,①体外实验：采用CCK-8法检测不同浓度的Od-Sb对HepG2/ADM的影响；克隆形成实验检测Od-Sb对HepG2/ADM克隆形成能力的影响；流式细胞术检测Od-Sb对HepG2/ADM凋亡的影响；Western blot检测Od-Sb对HepG2/ADM中Ki-67、Bcl-2蛋白表达的影响。②体内实验：以裸鼠HepG2/ADM皮下移植瘤为模型，观察Od-Sb对瘤体的作用，并采用免疫组化法检测Ki-67、Bcl-2蛋白的表达。,结果,2,①体外实验显示，与对照组比较，Od-Sb可以抑制HepG2/ADM细胞的增殖，抑制HepG2/ADM细胞的克隆形成，促进其凋亡，并下调Ki-67、Bcl-2蛋白的表达（,P,<,0.05）。②体内实验显示，与对照组比较，Od-Sb可以抑制裸鼠HepG2/ADM皮下移植瘤瘤体的生长，下调Ki-67、Bcl-2蛋白的表达（,P,<,0.05，,P,<,0.001）。,结论,2,Od-Sb可下调HepG2/ADM 中Ki-67、Bcl-2蛋白的表达，抑制HepG2/ADM的生长，并促进其凋亡；Od-Sb通过增殖-凋亡调控机制部分逆转HepG2/ADM的耐药。

Abstract

Objective,2,To study the effects of Oldenlandia diffusa roxb and Scutellariae barbatae herba (Od-Sb) on the proliferation and apoptosis of HepG2/ADM.,Methods,2,①In vitro experiment: the effect of different concentrations of Od-Sb on the survival rate of HepG2/ADM was detected by CCK8 assay; the effect of Od-Sb on HepG2/ADM clonal formation ability was detected by cloning formation experiment; the effect of Od-Sb on the apoptosis of HepG2/ADM was detected by flow cytometry; the effect of Od-Sb on the protein expression of Ki-67 and Bcl-2 was detected by Western blot. ②In vivo experiment: the subcutaneous transplanted tumor of HepG2/ADM in nude mice was used as a model to observe the inhibitory effect of Od-Sb on the tumor, and the proteins expression of Ki-67 and Bcl-2 was detected by immunohistochemistry.,Results,2,①In vitro experiments, it was showed that compared with the control group, Od-Sb could inhibit the proliferation of HepG2/ADM cells, inhibit the formation of HepG2/ADM cells, promote its apoptosis, and down-regulated the expression of Ki-67 and Bcl-2 proteins (,P,<,0.05) . ② In vivo experiments showed that compared with the control group, Od-Sb inhibited the growth of HepG2/ADM subcutaneous transplanted tumor body, and down-regulated the expression of Ki-67 and Bcl-2 proteins (,P,<,0.05,P,<,0.001) .,Conclusion,2,Od-Sb can down-regulate the expression of Ki-67 and Bcl-2 proteins, inhibit the growth of HepG2/ADM and promote its apoptosis. Od-Sb can partially reverse the resistance of HepG2/ADM through the mechanism of proliferation-apoptosis regulation.

关键词

白花蛇舌草半枝莲肝细胞癌阿霉素耐药模型小鼠中药研究

Keywords

Oldenlandia diffusa roxbScutellariae barbata herbahepatocellular carcinomaadrimycindrug resistancemodel micetraditional Chinese herbal medicine research

references

SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2021, 71 (3): 209-249.

原发性肝癌诊疗规范编写专家委员会. 原发性肝癌诊疗规范（2019年版）[J]. 中国临床医学， 2020, 27(1): 140-160.

王宇翾. 原发性肝癌患者综合治疗的研究进展[J]. 中国疗养医学，2020, 29(8): 817-819.

赵可新，王伟刚，沈国华，等. 阿霉素耐药逆转研究[J]. 中国医药导报，2006, 3(35): 7-9.

LONGLEY D B, JOHNSTON P G. Molecular mechanisms of drug resistance[J]. J Pathol, 2005, 205 (2): 275-292.

李起，刘作金，张俊，等. 中药复方肝癌-1号逆转肝癌多药耐药的实验研究[J]. 消化外科， 2006, 5(1): 70-73.

谢正元，赖月亮，刘思甫，等. 槐耳颗粒逆转肝癌侧群细胞耐阿霉素的实验研究[J]. 南昌大学学报，2020, 60 (5): 13-16.

曹聪，黄桂柳，黄赞松，等. 姜黄素对肝癌耐药细胞HepG2/ADM的增殖和阿霉素耐药性的影响[J]. 广西医学，2020, 42(8): 976-980.

钱丽丽，赵向丽，冯晓军，等. 原发性肝癌证型分布及用药分析[J]. 河南中医，2018, 38(8): 1189-1193.

闫辉，吕青涛. 白花蛇舌草、半枝莲及其药对抗肿瘤活性的研究进展[J]. 现代肿瘤医学，2015, 23(22): 3353-3356.

郭姗，邢佳欣，赵瑞君，等. 肝癌耐药细胞株Bel-7402/ADM的建立以及家蝇幼虫抗菌肽对其耐药性逆转作用的研究[J]. 寄生虫与医学昆虫学报，2017, 24 (3): 161-168.

黄继汉，黄晓晖，陈志扬，等. 药理试验中动物间和动物与人体间的等效剂量换算[J]. 中国临床药理学与治疗学，2004, 9(9): 1069-1072.

赫淑倩，成玉霞，綦黄鹏，等. 子宫内膜癌198例临床病理特征及预后影响因素分析[J]. 中华肿瘤防治杂志，2019, 26(20): 1562-1568.

侯倩，赵海鸥，于海，等. 弥漫性大B细胞性淋巴瘤中bcl-2表达与基因重排的相关性[J]. 诊断病理学杂志，2019, 26(6): 364-368.

郑荣寿，左婷婷，曾红梅，等. 中国肝癌死亡状况与生存分析[J]. 中华肿瘤杂志，2015, 37(9): 697-702.

CARVALHO C, SANTOS R X, CARDOSO S, et al. Doxorubicin: the good, the bad and the ugly effect[J]. Curr Med Chem, 2009, 16 (25): 3267-3285.

PABLA N, DONG Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies[J]. Kidney Int, 2008, 73 (9): 994-1007.

HARTMANN J T, HAAP M, KOPP H G, et al. Tyrosine kinase inhibitors-a review on pharmacology, metabolism and side effects[J]. Curr Drug Metab, 2009, 10(5): 470-481.

NOBILI S, LANDINI I, MAZZEI T, et al. Overcoming tumor multidrug resistance using drugs able to evade P-glycoprotein or to exploit its expression[J]. Med Res Rev, 2012, 32 (6): 1220-1262.

SHUKLA S W C P, AMBUDKAR S V. Development of inhibitors of ATP-binding cassette drug transporters: present status and challenges[J]. Expert Opin Drug Metab Toxicol, 2008, 4 (2): 205-223.

SHUKLA S O S, AMBUDKAR S V. Improving cancer chemotherapy with modulators of ABC drug transporters[J]. Curr Drug Targets, 2011, 12 (5): 621-630.

靳祎祎，严兆坤，赖子君，等. 白花蛇舌草对大肠癌耐药移植瘤细胞凋亡的影响[J]. 现代中西医结合杂志，2017, 26(12): 1255-1258.

赵诗云，尹小明，吴东风，等. 白花蛇舌草水提取物对多药耐药白血病细胞HL-60/ADR的作用[J]. 四川中医，2010, 28(2): 55-57.

廖作庄，韦丽美，徐灵源，等. 白花蛇舌草注射液逆转人肝癌细胞BEL-7402/5-FU的多药耐药作用[J]. 西安交通大学学报（医学版），2015, 36 (4): 554-557.

岳红刚，袁丹迪，李露霞. 半枝莲对5-FU治疗晚期大肠癌的疗效及血清miRNA-34a表达水平的影响[J]. 南昌大学学报（医学版），2019, 59(3): 68-71.

李锦梅，李丹丹，严威，等. 半枝莲新克罗烷型二萜成分逆转肿瘤多药耐药活性研究[J]. 天然产物研究与开发，2020, 32(3): 365-372.

LIU Y, YIN W, YAN T, et al. The clinical significance of Ki-67 as a marker of prognostic value and chemosensitivity prediction in hormone-receptor-positive breast cancer: a meta-analysis of the published literature[J]. Curr Med Res Opin, 2013, 29 (11): 1453-1461.

IMAMURA Y, MUKOHARA T, SHIMONO Y, et al. Comparison of 2D-and 3D-culture models as drug-testing platforms in breast cancer[J]. Oncol Rep, 2015, 33 (4): 1837-1843.

李正东，傅韵，成晓林，等. siRNA抑制Ki-67表达对乳腺癌MCF-7/ADR细胞阿霉素耐药性的研究[J]. 同济大学学报（医学版），2011, 32(3): 11-14.

GOLDAR S, KHANIANI M S, DERAKHSHAN S M, et al. Molecular mechanisms of apoptosis and roles in cancer development and treatment[J]. Asian Pac J Cancer Prev, 2015, 16 (6): 2129-2144.

MAJI S, PANDA S, SAMAL S K, et al. Bcl-2 antiapoptotic family proteins and chemoresistance in cancer [J]. Adv Cancer Res, 2018(137): 37-75.

INDRAN I R, TUFO G, PERVAIZ S, et al. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells[J]. Biochim Biophys Acta, 2011, 1807 (6): 735-745.

FEENSTRA I, VISSERS L E, ORSEL M, et al. Genotype-phenotype mapping of chromosome 18q deletions by high-resolution array CGH: an update of the phenotypic map[J]. Am J Med Genet A, 2007, 143A (16): 1858-1867.

OGURA T, TANAKA Y, TAMAKI H, et al. Docetaxel induces Bcl-2-and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells[J]. Int J Oncol, 2016, 48 (6): 2330-2338.

SUN Y, HU B, WANG Q, et al. Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR-216a[J]. Cell Death Dis, 2018, 9 (2): 85.

DONG J, ZHAO Y P, ZHOU L, et al. Bcl-2 upregulation induced by miR-21 via a direct interaction is associated with apoptosis and chemoresistance in MIA PaCa-2 pancreatic cancer cells[J]. Arch Med Res, 2011, 42 (1): 8-14.

ZHANG C, ZHAO Y, ZENG B. Enhanced chemosensitivity by simultaneously inhibiting cell cycle progression and promoting apoptosis of drug-resistant osteosarcoma MG63/DXR cells by targeting Cyclin D1 and Bcl-2[J]. Cancer Biomark, 2012, 12 (4): 155-167.

YANG F, LI Q J, GONG Z B, et al. MicroRNA-34a targets Bcl-2 and sensitizes human hepatocellular carcinoma cells to sorafenib treatment[J]. Technol Cancer Res Treat, 2014, 13 (1): 77-86.

ZHOU M, ZHANG Q, ZHAO J, et al. Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC[J]. Oncol Rep, 2017, 38 (3): 1742-1750.

浏览量

472

下载量

CSCD

CNKI被引量

文章被引用时，请邮件提醒。

提交

工具集

关联资源

左金丸逆转KRAS突变型大肠癌西妥昔单抗耐药的作用机制研究

辣椒素保护肠黏膜屏障改善酒精性肝病小鼠肝损伤的实验研究

当归芍药散对高脂饮食诱导的非酒精性脂肪肝小鼠模型的影响

自拟益气化瘀补肾方对膝骨关节炎小鼠β-catenin信号通路的影响

辛前甘桔汤对慢性鼻窦炎小鼠lncRNA SNHG16、EGFR及MUC5AC mRNA表达的影响