Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Sorafenib suppresses the epithelial-mesenchymal transition of hepatocellular carcinoma cells after insufficient radiofrequency ablation

Authors: Shuying Dong, Jian Kong, Fandong Kong, Jinge Kong, Jun Gao, Liang Ji, Bing Pan, Lian Chen, Lemin Zheng, Wenbing Sun

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Epithelial-mesenchymal transition (EMT) played an important role in the progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA). However, whether sorafenib could be used to suppress the EMT of HCC after insufficient RFA and further prevent the progression of residual HCC remains poorly unknown.

Methods

Insufficient RFA was simulated using a water bath (47 °C 5, 10, 15, 20 and 25 min gradually). MTT assay and transwell assay were used to evaluate the effects of sorafenib on viability, migration and invasion of HepG2 and SMMC7721 cells after insufficient RFA in vitro. After insufficient RFA, the molecular changes in HCC cells with the treatment of sorafeinb were evaluated using western blot and ELISAs. An ectopic nude mice model was used to evaluate the effect of sorafenib on the growth of HepG2 cells in vivo after insufficient RFA.

Results

HepG2 and SMMC7721 cells after insufficient RFA (named as HepG2-H and SMMC7721-H) exhibited enhanced viability, migration and invasion in vitro. Sorafenib inhibited the enhanced viability, migration and invasion of HepG2 and SMMC7721 cells after insufficient RFA. Molecular changes of EMT were observed in HepG2-H and SMMC7721-H cells. Sorafenib inhibited the EMT of HepG2-H and SMMC7721-H cells. HepG2-H cells also exhibited larger tumor size in vivo. Higher expression of PCNA, Ki67, N-cadherin, MMP-2 and MMP-9, was also observed in HepG2-H tumors. Sorafenib blocked the enhanced growth of HepG2 cells in vivo after insufficient RFA.

Conclusions

Sorafenib inhibited the EMT of HCC cells after insufficient RFA, and may be used to prevent the progression of HCC after RFA.
Appendix
Available only for authorised users
Literature
1.
2.
Lee DH, Lee JM, Lee JY, Kim SH, Yoon JH, Kim YJ, et al. Radiofrequency ablation of hepatocellular carcinoma as first-line treatment: long-term results and prognostic factors in 162 patients with cirrhosis. Radiology. 2014;270(3):900–9.CrossRefPubMed
3.
Nijkamp MW, van der Bilt JD, de Bruijn MT, Molenaar IQ, Voest EE, van Diest PJ, et al. Accelerated perinecrotic outgrowth of colorectal liver metastases following radiofrequency ablation is a hypoxia-driven phenomenon. Ann Surg. 2009;249(5):814–23.CrossRefPubMed
4.
Seki T, Tamai T, Ikeda K, Imamura M, Nishimura A, Yamashiki N, et al. Rapid progression of hepatocellular carcinoma after transcatheter arterial chemoembolization and percutaneous radiofrequency ablation in the primary tumour region. Eur J Gastroenterol Hepatol. 2001;13(3):291–4.CrossRefPubMed
5.
Ruzzenente A, Manzoni GD, Molfetta M, Pachera S, Genco B, Donataccio M, et al. Rapid progression of hepatocellular carcinoma after Radiofrequency Ablation. World journal of gastroenterology : WJG. 2004;10(8):1137–40.PubMedPubMedCentral
6.
Shiozawa K, Watanabe M, Takahashi M, Wakui N, Iida K, Sumino Y. Analysis of patients with rapid aggressive tumor progression of hepatocellular carcinoma after percutaneous radiofrequency ablation. Hepatogastroenterology. 2009;56(96):1689–95.PubMed
7.
Obara K, Matsumoto N, Okamoto M, Kobayashi M, Ikeda H, Takahashi H, et al. Insufficient radiofrequency ablation therapy may induce further malignant transformation of hepatocellular carcinoma. Hepatol Int. 2008;2(1):116–23.CrossRefPubMedPubMedCentral
8.
Ke S, Ding XM, Kong J, Gao J, Wang SH, Cheng Y, et al. Low temperature of radiofrequency ablation at the target sites can facilitate rapid progression of residual hepatic VX2 carcinoma. J Transl Med. 2010;8:73.CrossRefPubMedPubMedCentral
9.
Kong J, Kong J, Pan B, Ke S, Dong S, Li X, et al. Insufficient radiofrequency ablation promotes angiogenesis of residual hepatocellular carcinoma via HIF-1alpha/VEGFA. PLoS One. 2012;7(5), e37266.CrossRefPubMedPubMedCentral
10.
Kong J, Kong L, Kong J, Ke S, Gao J, Ding X, et al. After insufficient radiofrequency ablation, tumor-associated endothelial cells exhibit enhanced angiogenesis and promote invasiveness of residual hepatocellular carcinoma. J Transl Med. 2012;10:230.CrossRefPubMedPubMedCentral
11.
Dong S, Kong J, Kong F, Kong J, Gao J, Ke S, et al. Insufficient radiofrequency ablation promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through Akt and ERK signaling pathways. J Transl Med. 2013;11:273.CrossRefPubMedPubMedCentral
12.
Yoshida S, Kornek M, Ikenaga N, Schmelzle M, Masuzaki R, Csizmadia E, et al. Sublethal heat treatment promotes epithelial-mesenchymal transition and enhances the malignant potential of hepatocellular carcinoma. Hepatology. 2013;58(5):1667–80.CrossRefPubMed
13.
De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013;13(2):97–110.CrossRefPubMed
14.
Chen YL, Lv J, Ye XL, Sun MY, Xu Q, Liu CH, et al. Sorafenib inhibits transforming growth factor beta1-mediated epithelial-mesenchymal transition and apoptosis in mouse hepatocytes. Hepatology. 2011;53(5):1708–18.CrossRefPubMed
15.
Nagai T, Arao T, Furuta K, Sakai K, Kudo K, Kaneda H, et al. Sorafenib inhibits the hepatocyte growth factor-mediated epithelial mesenchymal transition in hepatocellular carcinoma. Mol Cancer Ther. 2011;10(1):169–77.CrossRefPubMed
16.
Chen YL, Zhang X, Bai J, Gai L, Ye XL, Zhang L, et al. Sorafenib ameliorates bleomycin-induced pulmonary fibrosis: potential roles in the inhibition of epithelial-mesenchymal transition and fibroblast activation. Cell death & disease. 2013;4, e665.CrossRef
17.
Zhang J, Chen YL, Ji G, Fang W, Gao Z, Liu Y, et al. Sorafenib inhibits epithelial-mesenchymal transition through an epigenetic-based mechanism in human lung epithelial cells. PLoS One. 2013;8(5), e64954.CrossRefPubMedPubMedCentral
18.
Feng YX, Wang T, Deng YZ, Yang P, Li JJ, Guan DX, et al. Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model. Hepatology. 2011;53(2):483–92.CrossRefPubMed
19.
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6), e1000412.CrossRefPubMedPubMedCentral
20.
Chang RM, Yang H, Fang F, Xu JF, Yang LY. miR-331-3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PHLPP. Hepatology. 2014.
21.
Liu L, Dai Y, Chen J, Zeng T, Li Y, Chen L, et al. Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3beta/Snail signaling. Hepatology. 2014;59(2):531–43.CrossRefPubMed
22.
Bao L, Yan Y, Xu C, Ji W, Shen S, Xu G, et al. MicroRNA-21 suppresses PTEN and hSulf-1 expression and promotes hepatocellular carcinoma progression through AKT/ERK pathways. Cancer Lett. 2013;337(2):226–36.CrossRefPubMed
23.
Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol. 2013;10(3):143–53.CrossRefPubMed
24.
25.
Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5(10):835–44.CrossRefPubMed
26.
Chen KF, Yu HC, Liu TH, Lee SS, Chen PJ, Cheng AL. Synergistic interactions between sorafenib and bortezomib in hepatocellular carcinoma involve PP2A-dependent Akt inactivation. J Hepatol. 2010;52(1):88–95.CrossRefPubMed
27.
Gedaly R, Angulo P, Hundley J, Daily MF, Chen C, Koch A, et al. PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Anticancer Res. 2010;30(12):4951–8.PubMedPubMedCentral
28.
Shimizu S, Takehara T, Hikita H, Kodama T, Tsunematsu H, Miyagi T, et al. Inhibition of autophagy potentiates the antitumor effect of the multikinase inhibitor sorafenib in hepatocellular carcinoma. International journal of cancer Journal international du cancer. 2012;131(3):548–57.CrossRefPubMed
29.
Fukuda H, Numata K, Moriya S, Shimoyama Y, Ishii T, Nozaki A, et al. Hepatocellular Carcinoma: Concomitant Sorafenib Promotes Necrosis after Radiofrequency Ablation-Propensity Score Matching Analysis. Radiology. 2014;131640.
30.
Li Y, Zheng YB, Zhao W, Liu B, Hu BS, He X, et al. Sorafenib in combination with transarterial chemoembolization and radiofrequency ablation in the treatment for unresectable hepatocellular carcinoma. Med Oncol. 2013;30(4):730.CrossRefPubMed
31.
Xu M, Xie XH, Xie XY, Xu ZF, Liu GJ, Zheng YL, et al. Sorafenib suppresses the rapid progress of hepatocellular carcinoma after insufficient radiofrequency ablation therapy: an experiment in vivo. Acta Radiol. 2013;54(2):199–204.CrossRefPubMed
32.
Boudou-Rouquette P, Narjoz C, Golmard JL, Thomas-Schoemann A, Mir O, Taieb F, et al. Early sorafenib-induced toxicity is associated with drug exposure and UGTIA9 genetic polymorphism in patients with solid tumors: a preliminary study. PLoS One. 2012;7(8), e42875.CrossRefPubMedPubMedCentral
33.
Kong J, Kong F, Gao J, Zhang Q, Dong S, Gu F, et al. YC-1 enhances the anti-tumor activity of sorafenib through inhibition of signal transducer and activator of transcription 3 (STAT3) in hepatocellular carcinoma. Mol Cancer. 2014;13:7.CrossRefPubMedPubMedCentral
Metadata
Title
Sorafenib suppresses the epithelial-mesenchymal transition of hepatocellular carcinoma cells after insufficient radiofrequency ablation
Authors
Shuying Dong
Jian Kong
Fandong Kong
Jinge Kong
Jun Gao
Liang Ji
Bing Pan
Lian Chen
Lemin Zheng
Wenbing Sun
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1949-7

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Research article

Perceived causes and consequences of sexual changes after cancer for women and men: a mixed method study

Research article

Total and partial cancer prevalence in the adult French population in 2008

Study protocol

BEV-IP: Perioperative chemotherapy with bevacizumab in patients undergoing cytoreduction and intraperitoneal chemoperfusion for colorectal carcinomatosis

Research article

Multicenter phase II study of FOLFIRI plus bevacizumab after discontinuation of oxaliplatin-based regimen for advanced or recurrent colorectal cancer (CR0802)

Research article

Gene expression profiling leads to discovery of correlation of matrix metalloproteinase 11 and heparanase 2 in breast cancer progression

Study protocol

TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG)
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits