oru.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Conditioned media from human macrophages of M1 phenotype attenuate the cytotoxic effect of 5-fluorouracil on the HT-29 colon cancer cell line
Department of Health Sciences, Karlstad University, Karlstad, Sweden.
Department of Health Sciences, Karlstad University, Karlstad, Sweden.
Örebro University, School of Medicine, Örebro University, Sweden.
Department of Health Sciences, Karlstad University, Karlstad, Sweden.
2015 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 46, no 1, p. 37-46Article in journal (Refereed) Published
Abstract [en]

Resistance of tumor cells to chemotherapy, such as 5-fluorouracil (5-FU), is an obstacle for successful treatment of cancer. As a follow-up of a previous study we have investigated the effect of conditioned media (CM) from macrophages of M1 or M2 phenotypes on 5-FU cytotoxicity on the colon cancer cell lines HT-29 and CACO-2. HT-29 cells, but not CACO-2 cells, having been treated with a combination of M1 CM and 5-FU recovered their cell growth to a much larger extent compared to cells having been treated with 5-FU alone when further cultured for 7 days in fresh media. M1 CM treatment of HT-29, but not CACO-2 cells, induced cell cycle arrest in the G(0)/G(1) and G(2)/M phases. 5-FU treatment induced accumulation of cells in S-phase in both HT-29 and CACO-2 cells. This accumulation of cells in S-phase was attenuated by combined M1 CM and 5-FU treatment in HT-29 cells, but not in CACO-2 cells. The mRNA expression of cell cycle regulatory proteins and 5-FU metabolic enzymes were analyzed in an attempt to find possible mechanisms for the M1 CM induced attenuation of 5-FU cytotoxicity in HT-29. Thymidylate synthetase (TS) and thymidine phosphorylase (TP) were found to be substantially downregulated and upregulated, respectively, in HT-29 cells treated with M1 CM, making them unlikely as mediators of reduced 5-FU cytotoxicity. Among cell cycle regulating proteins, p21 was induced in HT-29 cells, but not in CACO-2 cells, in response to M1 CM treatment. However, small interfering RNA (siRNA) knockdown of p21 had no effect on the M1 CM induced cell cycle arrest seen in HT-29 and neither did it change the growth recovery after combined treatment of HT-29 cells with M1 CM and 5-FU. In conclusion, treatment of HT-29 cells with M1 CM reduces the cytotoxic effect of 5-FU and this is mediated by a M1 CM induced cell cycle arrest in the G(0)/G(1) and G(2)/M phases. So far, we lack an explanation why this action is absent in the CACO-2 cells. The current findings may be important for optimization of chemotherapy in colon cancer.

Place, publisher, year, edition, pages
Athens, Greece: Spandidos Publications , 2015. Vol. 46, no 1, p. 37-46
Keywords [en]
Chemotherapy, 5-fluorouracil, colon cancer cell line, HT-29, CACO-2, M1 macrophages, M2 macrophages, cell cycle
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-40154DOI: 10.3892/ijo.2014.2696ISI: 000345885900004PubMedID: 25310018Scopus ID: 2-s2.0-84917710504OAI: oai:DiVA.org:oru-40154DiVA, id: diva2:776904
Note

Funding Agencies:

County Council of Värmland

Örebro University

Available from: 2015-01-08 Created: 2015-01-07 Last updated: 2017-12-05Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Delbro, Dick

Search in DiVA

By author/editor
Hedbrant, AlexanderErlandsson, AnnDelbro, Dick
By organisation
School of Medicine, Örebro University, Sweden
In the same journal
International Journal of Oncology
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 90 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf