Differential protein expression and novel biomarkers related to 5-FU resistance in a 3D colorectal adenocarcinoma model

Sang Hak Lee, Jae Kok Nam, Jong Kok Park, Joo Ho Lee, Do Sik Min, Hyo Jeong Kuh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The multicellular spheroid (MCS) is an in vitro model which is highly representative of the avascular region of solid tumors by reflecting microenvironmental conditions in vivo. Hence, it is considered the most appropriate model for studying drug resistance. We compared chemosensitivity to 5-fluorouracil (5-FU) and differential protein expression between the 3D MCS model and the 2D monolayers using DLD-1 cells. We analyzed several significant signaling molecules through western blot analysis. Although various changes in the expression level were observed depending on the samples, we did not obtained remarkable findings. Notably, the level of p-mTOR decreased upon 5-FU exposure in the monolayers, while its level was higher in the MCSs. Nine novel proteins were identified by 2-DE and MALDI-TOF analysis for exhibiting differential expression between the MCS model and the monolayers. Among these, collapsin response mediator protein 2 (CRMP-2), DNA replication complex GINS protein PSF2 (PSF-2) and selenium-binding protein 1 (SBP-1) were notable not only for their differential expression but also for decreased expression following 5-FU exposure, indicating their possible roles as novel biomarkers for sensitivity (CRMP-2, PSF-2) as well as resistance (SBP-1) to 5-FU. Overall, the present study demonstrated greater 5-FU resistance in human colorectal cancer cells grown as MCSs compared to monolayers and identified p-mTOR, CRMP-2, PSF-2 and SBP-1 as novel potential biomarkers of 5-FU chemosensitivity/resistance for human colorectal cancer, findings which warrant further investigation.

Original languageEnglish
Pages (from-to)1427-1434
Number of pages8
JournalOncology Reports
Volume32
Issue number4
DOIs
Publication statusPublished - 2014 Oct

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Fluorouracil
Selenium-Binding Proteins
Adenocarcinoma
Biomarkers
Cellular Spheroids
Proteins
Colorectal Neoplasms
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
DNA Replication
Drug Resistance
Western Blotting
collapsin response mediator protein-2
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lee, Sang Hak ; Nam, Jae Kok ; Park, Jong Kok ; Lee, Joo Ho ; Min, Do Sik ; Kuh, Hyo Jeong. / Differential protein expression and novel biomarkers related to 5-FU resistance in a 3D colorectal adenocarcinoma model. In: Oncology Reports. 2014 ; Vol. 32, No. 4. pp. 1427-1434.
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Differential protein expression and novel biomarkers related to 5-FU resistance in a 3D colorectal adenocarcinoma model. / Lee, Sang Hak; Nam, Jae Kok; Park, Jong Kok; Lee, Joo Ho; Min, Do Sik; Kuh, Hyo Jeong.

In: Oncology Reports, Vol. 32, No. 4, 10.2014, p. 1427-1434.

Research output: Contribution to journalArticle

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AU - Nam, Jae Kok

AU - Park, Jong Kok

AU - Lee, Joo Ho

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AU - Kuh, Hyo Jeong

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