Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism

MENG Xiaoyi; YANG Jianhua; WEN Limei; Ayiziba·Tuerhong; HU Junping

doi:10.6039/j.issn.1001-0408.2024.03.04

您当前的位置：

首页 >

文章列表页 >

Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism

更新时间：2024-02-07

- Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism
- ZHONGGUO YAOFANG Vol. 35, Issue 3, Pages: 283-289(2024)
- 作者机构：
  
  1.新疆医科大学药学院，乌鲁木齐　830017
  2.新疆医科大学第一附属医院药学部，乌鲁木齐　830054
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.03.04
  CLC： R965
- Published：15 February 2024，
  
  Received：01 September 2023，
  
  Revised：16 January 2024，
扫描看全文
孟小艺,杨建华,文丽梅等.护肝布祖热方联合奥沙利铂对肝细胞癌荷瘤裸鼠的减毒增效作用及机制 ^Δ[J].中国药房,2024,35(03):283-289.

MENG Xiaoyi,YANG Jianhua,WEN Limei,et al.Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism[J].ZHONGGUO YAOFANG,2024,35(03):283-289.
孟小艺,杨建华,文丽梅等.护肝布祖热方联合奥沙利铂对肝细胞癌荷瘤裸鼠的减毒增效作用及机制 ^Δ[J].中国药房,2024,35(03):283-289. DOI： 10.6039/j.issn.1001-0408.2024.03.04.

MENG Xiaoyi,YANG Jianhua,WEN Limei,et al.Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism[J].ZHONGGUO YAOFANG,2024,35(03):283-289. DOI： 10.6039/j.issn.1001-0408.2024.03.04.

摘要

目的

研究护肝布祖热方联合奥沙利铂对肝细胞癌荷瘤裸鼠的减毒增效作用及机制。

方法

从40只裸鼠中选取8只作为空白组（生理盐水），其余32只裸鼠皮下接种人肝癌Huh7细胞构建荷瘤裸鼠模型。将造模成功的32只裸鼠随机分为模型组（生理盐水，灌胃）、奥沙利铂组（10 mg/kg，腹腔注射）、护肝布祖热方组（0.69 g/kg，灌胃）和联合用药组（腹腔注射10 mg/kg奥沙利铂+灌胃0.69 g/kg护肝布祖热方浸膏），每组8只。每天灌胃给药/生理盐水1次，连续32 d；每7天腹腔注射给药1次，共5次。实验期间，观察各组裸鼠一般情况，每4 d测量1次肿瘤体积；给药第30天，检测裸鼠热刺激缩足潜伏期；给药结束后，检测各组裸鼠的抑瘤率、脾脏系数、血常规指标以及血清中天冬氨酸转氨酶（AST）和肌酐水平，观察裸鼠肿瘤组织病理形态变化，检测肿瘤组织中微管相关蛋白1轻链3（LC3）、选择性自噬接头蛋白p62、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）和胱天蛋白酶3（Caspase-3）的表达。

结果

与模型组比较，奥沙利铂组裸鼠肿瘤体积、瘤重以及全血中白细胞、红细胞数量和脾脏系数均显著减小/降低（

＜0.01），热刺激缩足潜伏期和血清中AST、肌酐水平均显著延长/升高（

＜0.05或

＜0.01）。与奥沙利铂组比较，联合用药组裸鼠肿瘤体积、瘤重均显著减小/降低（

＜0.01），全血中白细胞、红细胞、血小板数量和脾脏系数均显著增加/升高（

＜0.05或

＜0.01），热刺激缩足潜伏期和血清中AST、肌酐水平均显著缩短/降低（

＜0.01）；肿瘤组织中LC3、Bax和Caspase-3蛋白的表达水平均显著升高（

＜0.01），p62、Bcl-2蛋白的表达水平均显著降低（

＜0.01）。

结论

护肝布祖热方通过诱导凋亡和自噬增强奥沙利铂对裸鼠的抑瘤作用，并可缓解奥沙利铂引起的外周神经毒性、血液毒性、肝肾毒性和免疫器官毒性。

Abstract

OBJECTIVE

To investigate the attenuation and synergism of Hugan buzure recipe （HBR） combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism.

METHODS

Eight nude mice were selected from 40 nude mice as the blank group （normal saline）， and the remaining nude mice were inoculated with hepatoma cells Huh7 to establish the tumor-bearing model. The 32 modeled nude mice were randomly allocated to four groups： model group （normal saline， ig）， HBR group （0.69 g/kg， ig）， oxaliplatin group （10 mg/kg， ip）， and combination group （intraperitoneal injection of 0.69 g/kg HBR+intragastric administration of 10 mg/kg oxaliplatin）， with 8 mice in each group. Administer drug/normal saline once a day for 32 consecutive days； administer subcutaneous injection once every 7 days for a total of 5 times. During the experiment， the general condition of nude mice in each group was observed， and the tumor volume was measured every 4 days. On the 30th day of administration， the thermal stimulation paw withdrawal latency of nude mice in each group were detected. The tumor inhibition rate， spleen coefficient， the number of red blood cells， white blood cells and platelets in the whole blood of nude mice in each group， and the content of aspartate aminotransferase （AST） and creatinine in serum were detected after the end of administration. HE staining was used to observe the pathological changes in tumor tissues in nude mice in each group. The expression of microtubule-associated protein 1 light chain 3 （LC3）， selective autophagy adaptor protein p62， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Caspase-3 protein in tumor tissues.

RESULT

Compared with the model group， the tumor volume， tumor weight， white blood cells， red blood cells in the whole blood and spleen coefficients of nude mice in the oxaliplatin group were significantly decreased （

＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly increased （

＜0.05 or

＜0.01）. Compared with the oxaliplatin group， the tumor volume and tumor weight of nude mice in the combination group were significantly decreased （

＜0.01）； the white blood cells， red blood cells and platelets in the whole blood and spleen coefficients of nude mice were significantly increased （

＜0.05 or

＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly decreased （

＜0.01）； the expression levels of LC3， Bax and Caspase-3 proteins in tumor tissues of nude mice were significantly increased （

＜0.01）， and the expression levels of p62 and Bcl-2 proteins were significantly decreased （

＜0.01）.

CONCLUSIONS

HBR enhances the tumor inhibition rate of oxaliplatin by inducing apoptosis and autophagy， and can alleviate the peripheral neurotoxicity， hematological toxicity， hepatorenal toxicity， and immune organ toxicity caused by oxaliplatin in nude mice.

关键词

护肝布祖热方奥沙利铂肝癌减毒增效凋亡自噬

Keywords

oxaliplatinhepatic cancerattenuation and synergismapoptosisautophagy

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.

PAN X W，HUANG J S，LIU S R，et al.Evaluation of the liver targeting and anti-liver cancer activity of artesunate-loaded and glycyrrhetinic acid-coated nanoparticles[J]. Exp Ther Med，2023，26（5）：516.

ZHANG C Y，XU C，GAO X Y，et al. Platinum-based drugs for cancer therapy and anti-tumor strategies[J]. Thera- nostics，2022，12（5）：2115-2132.

张燕，左国庆，汤为学.奥沙利铂对人肝癌细胞株HepG2体外增殖的影响[J].中华肝脏病杂志，2004，12（6）：374-375.

ZHANG Y，ZUO G Q，TANG W X. Study on apoptosis of human hepatoma cell line HepG2 induced by oxaliplatin[J]. Chin J Hepatol，2004，12（6）：374-375.

李媛媛，马泰，仲飞，等.奥沙利铂诱导的人肝癌细胞株HepG2自噬潮增加及其对细胞生存率的影响[J].肿瘤，2013，33（2）：132-137.

LI Y Y，MA T，ZHONG F，et al. The enhancement of autophagic flux induced by oxaliplatin in hepatocarcinoma cell line HepG2 and its influence on cell proliferation[J]. Tumor，2013，33（2）：132-137.

朱晨，刘东，张程亮，等.姜黄素及其类似物辅助奥沙利铂治疗的研究进展[J]. 中国医院药学杂志，2020，40（21）：2284-2288.

ZHU C，LIU D，ZHANG C L，et al. Study progress of curcumin and its analogues in oxaliplatin therapy[J]. Chin J Hosp Pharm，2020，40（21）：2284-2288.

杨爱琳，夏天吉，赵亚楠，等.槐耳清膏通过激活自噬抑制人肝癌细胞SK-HEP-1增殖[J]. 中国中药杂志，2018，43（3）：591-595.

YANG A L，XIA T J，ZHAO Y N，et al.Huaier aqueous extract inhibits proliferation of human hepatoma SK-HEP-1 cells through up-regulation of autophagy[J].China J Chin Mater Med，2018，43（3）：591-595.

ZHAO J Y，LIU L Y，ZHANG Y C，et al.The herbal mixture Xiao-Chai-hu Tang （xcht） induces apoptosis of human hepatocellular carcinoma huh7 cells in vitro and in vivo[J]. Afr J Tradit Complement Altern Med，2017，14（3）：231-241.

周熙祥，伍志伟，张录梅，等.贞芪扶正颗粒辅助奥沙利铂治疗H22移植瘤小鼠的疗效及其对Bax、Bcl-2表达的影响[J].中成药，2021，43（7）：1746-1752.

ZHOU X X，WU Z W，ZHANG L M，et al. Effect of Zhenqi fuzheng granules with oxaliplatin in the treatment for H22-bearing mice and the influences on Bax and Bcl-2 in tumor tissue[J]. Chin Tradit Pat Med，2021，43（7）：1746-1752.

朱晨，张程亮，杨金玉，等.槐耳颗粒缓解奥沙利铂诱导肝脏损伤的作用及机制研究[J]. 中国医院药学杂志，2021，41（17）：1723-1729.

ZHU C，ZHANG C L，YANG J Y，et al. Study on the effect and mechanism of Huaier granules in relieving oxaliplatin-induced liver injury[J]. Chin J Hosp Pharm，2021，41（17）：1723-1729.

MENG X Y，LI M，QIAO M，et al.Hugan buzure induces autophagy and apoptosis in hepatocellular carcinoma by inhibiting PI3K/Akt/mTOR signaling pathway[J].Evid Based Complement Alternat Med，2022，2022：1618491.

薛淑一，李明春，苗青，等. 白头翁皂苷B4对肝癌细胞Huh-7及其荷瘤裸鼠肿瘤的抑制作用及机制研究[J].中国药房，2019，30（5）：601-607.

XUE S Y，LI M C，MIAO Q，et al. Inhibitory effects and mechanism of anemoside B4 on hepatocellular carcinoma Huh-7 cells and tumor-bearing nude mice[J].China Pharm，2019，30（5）：601-607.

WANG Z，ZHOU J，FAN J，et al. Oxaliplatin induces apoptosis in hepatocellular carcinoma cells and inhibits tumor growth[J]. Expert Opin Investig Drugs，2009，18（11）：1595-1604.

邱泗安，姜秀清. 黄芪桂枝五物汤对奥沙利铂所致神经及血液毒性的治疗效果观察[J]. 山东医药，2014，54（6）：88-89.

QIU S A，JIANG X Q. Observation on therapeutic effect of Huangqi guizhi wuwu decoction on nerve and blood toxicity caused by oxaliplatin[J]. Shandong Med J，2014，54（6）：88-89.

顾莅冰，陈正鑫，蒋泽砚，等.参麦注射液协同奥沙利铂抗结肠肿瘤作用[J].天津中医药大学学报，2018，37（6）：449-454.

GU L B，CHEN Z X，JIANG Z Y，et al. Effect of Shenmai injection combined with oxaliplatin on colon cancer[J]. J Tianjin Univ Tradit Chin Med，2018，37（6）：449-454.

ILERITURK M，ILERITURK D，KANDEMIR O，et al. Naringin attenuates oxaliplatin-induced nephrotoxicity and hepatotoxicity：a molecular，biochemical，and histopathological approach in a rat model[J]. J Biochem Mol Toxicol，2023：e23604.

吴艾平，吴林龙，张红颖，等.加味黄芪桂枝五物汤抑制线粒体凋亡预防奥沙利铂周围神经毒性机制[J].西部医学，2023，35（2）：182-187.

WU A P，WU L L，ZHANG H Y，et al. Prevention of modified Huangqi Guizhi Wuwu decoction on inhibiting mitochondrial apoptosis mechanism of oxaliplatin peri- pheral neurotoxicity[J]. Med J West China，2023，35（2）：182-187.

GHOBRIAL I M，WITZIG T E，ADJEI A A. Targeting apoptosis pathways in cancer therapy[J]. CA Cancer J Clin，2005，55（3）：178-194.

塔玛莎·库尔曼江，王小静，李欣奕，等.异硫氰酸苄酯通过激活p53和AMPK-FOXO1a信号通路诱导宫颈癌细胞周期阻滞和凋亡[J].中国药理学通报，2024，（1）：114-125.

Tamasha·Kuermanjiang，WANG X J，LI X Y，et al. Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways[J]. Chin Pharmacol Bull，2024，（1）：114-125.

ZHONG P P，YANG H，LIN S，et al. A traditional Chinese medicine herb mixture Qingjie fuzheng granules inhibits hepatocellular carcinoma cells growth by inducing apoptosis[J]. J Evid Based Integr Med，2018，23：2515690X1878-9632.

JIANG T，HARDER B，ROJO DE LA VEGA M，et al.p62 links autophagy and Nrf2 signaling[J]. Free Radic Biol Med，2015，88（Pt B）：199-204.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanism of Simotang oral liquid in improving functional dyspepsia model rats

Effects and mechanism of astilbin on myocardial ischemia-reperfusion injury in rats

Effect and potential mechanism of Safflower polysaccharide on apoptosis and autophagy of human hepatocellular carcinoma cells

褐藻素诱导人宫颈癌 HeLa细胞的自噬作用机制研究

甲基莲心碱抗肿瘤药理作用及其分子机制研究进展

Related Author

ZHOU Sainan

FU Jia

ZHANG Jizhuo

GONG Ming

HAN Lu

CHEN Xinghua

LIANG Xiao

WANG Rui

Related Institution

Dept. of Spleen and Stomach Disease， the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine

Dept. of Cardiac Surgery， Beijing Shijitan Hospital Affiliated to Capital Medical University

Medical Research Center， Beijing Chaoyang Hospital Affiliated to Capital Medical University

Dept. of Cardiac Surgery， Beijing Anzhen Hospital Affiliated to Capital Medical University

College of Pharmacy， Heilongjiang University of Chinese Medicine

Address：8/F,129 Daping Main Street,Yuzhong District,Chongqing 400042,P.R.China
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰