Interleukin-8 is related to poor chemotherapeutic response and tumourigenicity in hepatocellular carcinoma

Copyright © 2013 Elsevier Ltd. All rights reserved..

AIM: Interleukin-8 (IL-8) has been suggested as a prognostic biomarker for human hepatocellular carcinoma (HCC), but its roles in HCC progression and drug resistance have not been studied. This study investigates the role and underlying mechanism of IL-8 in the chemoresistance and progressive growth of HCC.

METHODS: The change of chemosensitivity and proportion of side population in hepatoma cells was examined by cell growth and flow cytometric analyses after anti-cancer treatments or knockdown of IL-8. Expression of IL-8 and ATP-binding cassette (ABC) transporters in hepatoma cells, xenograft and clinical HCC tissues was determined by Western blot and immunohistochemical analyses. Tumourigenicity of hepatoma cells was evaluated in vivo after silencing IL-8 gene.

RESULTS: Treatment of hepatoma cells with anti-cancer drugs increased the production of IL-8 and its receptor, as well as the proportion of side population (SP). Exogenous IL-8 increased the SP fraction and expression of multidrug resistance-1, decreasing the drug sensitivity. Silencing of IL-8 gene decreased the ratio of SP cells and drug resistance properties. Both IL-8 and ABC transporters were highly expressed in xenograft and clinical HCC tissues, and knockdown of IL-8 significantly reduced tumour size in vivo.

CONCLUSION: Anti-cancer drug-induced IL-8 secretion increased the expression of ABC transporters and SP cells, promoting the growth of HCC in vitro. Thus IL-8 may be a potential therapeutic target in the treatment of HCC.

Medienart:

E-Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:50

Enthalten in:

European journal of cancer (Oxford, England : 1990) - 50(2014), 2 vom: 01. Jan., Seite 341-50

Sprache:

Englisch

Beteiligte Personen:

Park, Seo Young [VerfasserIn]
Han, Jiyou [VerfasserIn]
Kim, Jong Bin [VerfasserIn]
Yang, Man-Gil [VerfasserIn]
Kim, Yoon Jun [VerfasserIn]
Lim, Hee-Joung [VerfasserIn]
An, Su Yeon [VerfasserIn]
Kim, Jong-Hoon [VerfasserIn]

Links:

Volltext

Themen:

80168379AG
ATP-Binding Cassette Transporters
ATP-binding cassette transporter
Antineoplastic Agents
Doxorubicin
Drug resistance
Hepatocellular carcinoma
IL-8
Interleukin-8
Journal Article
P88XT4IS4D
Paclitaxel
Receptors, Interleukin-8
Research Support, Non-U.S. Gov't
Side population

Anmerkungen:

Date Completed 03.03.2014

Date Revised 10.04.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ejca.2013.09.021

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM232023956