Cepharanthine hydrochloride inhibits kidney and testicular metastases from hepatocellular carcinoma in xenograft tumor models in nude mice

Lida ZHANG; Xinhui FANG; Yuxiu YANG; Yangqiu BAI; Shuangyin HAN

doi:10.16016/j.1000-5404.201712207

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Cepharanthine hydrochloride inhibits kidney and testicular metastases from hepatocellular carcinoma in xenograft tumor models in nude mice

Basic Medicine | 更新时间：2026-01-09

- Cepharanthine hydrochloride inhibits kidney and testicular metastases from hepatocellular carcinoma in xenograft tumor models in nude mice
- Journal of Third Military Medical University Vol. 40, Issue 13, Pages: 1192-1197(2018)
- 作者机构：
  
  450003 郑州，郑州大学人民医院消化内科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81372405)
- DOI：10.16016/j.1000-5404.201712207
  CLC： R73-55;R73-37;R735.7
- Received：01 December 2017，
  
  Revised：2018-01-12，
  
  Published：15 July 2018
- 稿件说明：
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Lida ZHANG, Xinhui FANG, Yuxiu YANG, et al. Cepharanthine hydrochloride inhibits kidney and testicular metastases from hepatocellular carcinoma in xenograft tumor models in nude mice[J]. Journal of Third Military Medical University, 2018, 40(13): 1192-1197.
DOI：

Lida ZHANG, Xinhui FANG, Yuxiu YANG, et al. Cepharanthine hydrochloride inhibits kidney and testicular metastases from hepatocellular carcinoma in xenograft tumor models in nude mice[J]. Journal of Third Military Medical University, 2018, 40(13): 1192-1197. DOI： 10.16016/j.1000-5404.201712207.

摘要

目的

通过裸鼠肝原位移植荧光人肝癌细胞，观察肝癌细胞肾脏、睾丸转移情况，并探讨盐酸千金藤碱抑制肝癌细胞转移及其分子机制。

方法

采用慢病毒转染构建稳定表达荧光素酶基因的人肝癌细胞SMCC-7721-Luc。BALB/c裸鼠皮下接种SMCC-7721-Luc细胞，待肿瘤长至100 mm

左右，取皮下瘤植入裸鼠肝脏包膜，建立裸鼠原位肝癌模型。裸鼠腹腔注射盐酸千金藤碱，用小动物活体成像系统观察肝原位肿瘤肾脏、睾丸转移情况。给药21 d后，解剖取肿瘤组织，Western blot检测相关蛋白表达，同时取肝脏、肾脏、睾丸等组织，用10%中性甲醛固定，进行病理分析。

结果

构建的SMCC-7721-Luc细胞能稳定表达Luc基因，裸鼠肝原位接种该细胞后产生较强、稳定的荧光。活体成像系统显示盐酸千金藤碱能抑制裸鼠原位肝癌向肾脏、睾丸转移，与其降低MMP-7和N-cadherin蛋白表达，上调E-cadherin蛋白表达有关。

结论

盐酸千金藤碱通过调控MMP-7、N-cadherin和E-cadherin蛋白抑制原位肝癌向肾脏、睾丸转移。

Abstract

Objective

To observe the kidney and testicular metastases from hepatocellular carcinoma in nude mouse model by orthotopic transplantation of human liver cancer cells stably expressing reporter gene luciferase

and investigate the anti-metastatic effects of cepharanthine hydrochloride (CEH) and its molecular mechanism.

Methods

SMMC-7721 cells were transfected with luciferas

e gene mediated by lentiviral vector to prepare SMMC-7721-Luc cells. Then the obtained cells were inoculated subcutaneously into the back of BALB/c nude mice to establish xenograft tumor model of nude mice. Till the masses grow into a size of 100 mm

the masses were collected and cut into blocks of 2 mm×1 mm×1 mm

and then transplanted into the liver to establish orthotopic tumor model of liver cancer. The tumor growth and kidney and testicular metastases were observed in nude mice after intraperitoneal injection of CEH by bioluminescence imaging system. In 21 d after CEH injection

the tumor tissues were harvested for expression of related proteins by Western blotting

and the liver

kidneys and testis were collected and fixed with 10% neutral formaldehyde for pathological observation.

Results

The established SMMC-7721-Luc cells stably expressed luciferase gene

and produced strong and stable fluorescence after orthotopic transplantation in nude mice. The bioluminescence imaging system displayed that CEH significantly inhibited the kidney and testicular metastases of orthotopic liver tumor

which was associated with the down-regulation of MMP-7 and N-cadherin

and up-regulation of E-cadherin.

Conclusion

CEH significantly inhibits the kidney and testicular metastases from hepatocellular carcinoma by regulating MMP-7

N-cadherin and E-cadherin.

关键词

Keywords

references

GERMANO D, DANIELE B. Systemic therapy of hepato-cellular carcinoma: current status and future perspectives[J]. World J Gastroenterol, 2014, 20(12): 3087-3099. DOI:10.3748/wjg.v20.i12.3087.

RAY E M, SANOFF H K. Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions[J]. J Hepatocell Carcinoma, 2017, 4: 131-138. DOI:10.2147/JHC.S124366.

WANG E A, STEIN J P, BELLAVIA R J, et al. Treatment options for unresectable HCC with a focus on SIRT with Yttrium-90 resin microspheres[J]. Int J Clin Pract, 2017, 71(11): e12972. DOI:10.1111/ijcp.12972.

HUANG C Z, WANG Y F, ZHANG Y, et al. Cepharanthine hydrochloride reverses P-glycoprotein-mediated multidrug resistance in human ovarian carcinoma A2780/Taxol cells by inhibiting the PI3K/Akt signaling pathway[J]. Oncol Rep, 2017, 38(4): 2558-2564. DOI:10.3892/or.2017.5879.

JANG T Y, YEH M L. Hepatocellular carcinoma metastatic to kidney mimicking renal cell carcinoma[J]. Kaohsiung J Med Sci, 2017, 33(3): 161-162. DOI:10.1016/j.kjms.2016.10.009.

WANG C H, YANG S. Testicular metastasis from hepatocellular carcinoma[J]. Int J Urol, 2006, 13(7): 1033-1034. DOI:10.1111/j.1442-2042.2006.01470.x.

潘金飞, 陆才德, 彭淑牖, 等.原发性肝癌右肾转移1例报告[J].实用肿瘤杂志, 2003, 18(2):140-141.DOI:10.13267/j.cnki.syzlzz.2003.02.025.

PAN J F, LU C D, PENG S Y, et al. A case report of right kidney metastasis in primary liver cancer[J]. J Pract Oncol, 2003, 18(2):140-141. DOI:10.13267 /j.cnki.syzlzz.2003.02.025.

程仕光, 李清, 彭宇, 等. PD-L1基因多态性与肝癌易感性以及预后之间的关系[J].第三军医大学学报, 2017, 39(5):487-492.DOI:10.16016/j.1000-5404.201609157.

CHENG S G, LI Q, PENG Y, et al. Association of single nucleotide polymorphisms of programmed death-ligand 1 with liver cancer susceptibility and prognosis[J]. J Third Mil Med Univ, 2017, 39(5):487-492. DOI: 10.16016/j.1000-5404.201609157.

DARNE C, LU Y, SEVICK-MURACA EM. Small animal fluorescence and bioluminescence tomography: a review of approaches, algorithms and technology update[J]. Phys Med Biol, 2014, 59(1): R1-64. DOI:10.1088/0031-9155/59/1/R1.

Qin X, Hu X, Wu C, et al. Hepatocellular carcinoma cells carrying a multimodality reporter gene for fluorescence, biolu minescence, and magnetic resonance imaging in vitro and in vivo [J ] . Acad Radiol, 2016, 23(11): 1422-1430. DOI:10.1016/j.acra.2016.07.009..

赵秀文, 汪攀, 兰川, 等.缺氧对C57小鼠脑胶质瘤模型肿瘤形成及生存期的影响[J].第三军医大学学报, 2015, 37(7):611-615.DOI:10.16016/j.1000-5404.201410185.

ZHAO X W, WANG P, LAN C, et al.Hypoxia improves tumor formation but reduces survival time in C57 mice implanted with glioma GL261 cells[J]. J Third Mil Med Univ, 2015, 37(7):611-615.DOI: 10.16016/j.1000-5404.201410185.

RAO Q, YOU A, GUO Z, et al. Intrahepatic tissue implantation represents a favorable approach for establishing orthotopic transplantation hepatocellular carcinoma mouse models[J]. PLoS ONE, 2016, 11(1): e0148263. DOI:10.1371/journal.pone.0148263.

FUJIWARA K, KOYAMA K, SUGA K, et al. A (90)Y-labelled anti-ROBO1 monoclonal antibody exhibits antitumour activity against hepatocellular carcinoma xenografts during ROBO1-targeted radioimmunotherapy[J]. EJNMMI Res, 2014, 4: 29. DOI:10.1186/s13550-014-0029-3.

DU L, NING Z, LIU F, et al. Corepressor metastasis-associated protein 3 modulates epithelial-to-mesenchymal transition and metastasis[J]. Chin J Cancer, 2017, 36(1). DOI:10.1186/s40880-017-0193-8.

CAI W S, SHEN F, FENG Z, et al. Downregulation of CDK-8 inhibits colon cancer hepatic metastasis by regulating Wnt/β-catenin pathway[J]. Biomed Pharmacother, 2015, 74: 153-157. DOI:10.1016/j.biopha.2015.08.015.

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