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 language | English |
|---|---|
| Pages (from-to) | 1427-1434 |
| Number of pages | 8 |
| Journal | Oncology Reports |
| Volume | 32 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2014 Oct |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
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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 journal › Article
TY - JOUR
T1 - Differential protein expression and novel biomarkers related to 5-FU resistance in a 3D colorectal adenocarcinoma model
AU - Lee, Sang Hak
AU - Nam, Jae Kok
AU - Park, Jong Kok
AU - Lee, Joo Ho
AU - Min, Do Sik
AU - Kuh, Hyo Jeong
PY - 2014/10
Y1 - 2014/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84923068530&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923068530&partnerID=8YFLogxK
U2 - 10.3892/or.2014.3337
DO - 10.3892/or.2014.3337
M3 - Article
C2 - 25050539
AN - SCOPUS:84923068530
VL - 32
SP - 1427
EP - 1434
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 4
ER -