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Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts
BACKGROUND: Although targeted therapies have improved the clinical outcomes of cancer treatment, tumors resistance to targeted drug are often detected too late and cause mortality. CSE1L is secreted from tumor and its phosphorylation is regulated by ERK1/2. ERK1/2 is located downstream of various gr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467675/ https://www.ncbi.nlm.nih.gov/pubmed/26070816 http://dx.doi.org/10.1186/s12967-015-0553-6 |
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author | Lee, Woan-Ruoh Shen, Shing-Chuan Shih, Yi-Hsien Chou, Chia-Lun Tseng, Jonathan Te-Peng Chin, Szu-Ying Liu, Kao-Hui Chen, Yen-Chou Jiang, Ming-Chung |
author_facet | Lee, Woan-Ruoh Shen, Shing-Chuan Shih, Yi-Hsien Chou, Chia-Lun Tseng, Jonathan Te-Peng Chin, Szu-Ying Liu, Kao-Hui Chen, Yen-Chou Jiang, Ming-Chung |
author_sort | Lee, Woan-Ruoh |
collection | PubMed |
description | BACKGROUND: Although targeted therapies have improved the clinical outcomes of cancer treatment, tumors resistance to targeted drug are often detected too late and cause mortality. CSE1L is secreted from tumor and its phosphorylation is regulated by ERK1/2. ERK1/2 is located downstream of various growth factor receptors and kinases, the targets of most targeted drugs. Serum phospho-CSE1L may be a marker for monitoring the efficacy of targeted therapy. METHODS: We used mice tumor xenograft model to study the assay of serum phosphorylated CSE1L for early detecting the efficacy of targeted drugs. The phosphorylation status of CSE1L in vemurafenib and sorafenib treated tumor cells were assayed by immunoblotting with antibody against phosphorylated CSE1L. RESULTS: Ras activation increased phospho-CSE1L expression in B16F10 melanoma cells. Vemurafenib and sorafenib treatment did not significantly reduce the total CSE1L levels; however, they inhibited ERK1/2 and CSE1L phosphorylation in A375 melanoma cells and HT-29 colorectal cancer cells. In the melanoma xenograft model, serum phospho-CSE1L level declined 5 days after vemurafenib/sunitinib treatment and 3 days after sorafenib/lapatinib treatment in the HT-29 colon cancer xenograft model. Vemurafenib/sunitinib and sorafenib/lapatinib treatments resulted in tumor regression. CONCLUSIONS: Our results indicated that serum phospho-CSE1L is useful for early detecting the efficacy of targeted therapy in initial treatment and for monitoring emerging secondary drug resistance to facilitate timely therapeutic decision making. |
format | Online Article Text |
id | pubmed-4467675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44676752015-06-16 Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts Lee, Woan-Ruoh Shen, Shing-Chuan Shih, Yi-Hsien Chou, Chia-Lun Tseng, Jonathan Te-Peng Chin, Szu-Ying Liu, Kao-Hui Chen, Yen-Chou Jiang, Ming-Chung J Transl Med Research BACKGROUND: Although targeted therapies have improved the clinical outcomes of cancer treatment, tumors resistance to targeted drug are often detected too late and cause mortality. CSE1L is secreted from tumor and its phosphorylation is regulated by ERK1/2. ERK1/2 is located downstream of various growth factor receptors and kinases, the targets of most targeted drugs. Serum phospho-CSE1L may be a marker for monitoring the efficacy of targeted therapy. METHODS: We used mice tumor xenograft model to study the assay of serum phosphorylated CSE1L for early detecting the efficacy of targeted drugs. The phosphorylation status of CSE1L in vemurafenib and sorafenib treated tumor cells were assayed by immunoblotting with antibody against phosphorylated CSE1L. RESULTS: Ras activation increased phospho-CSE1L expression in B16F10 melanoma cells. Vemurafenib and sorafenib treatment did not significantly reduce the total CSE1L levels; however, they inhibited ERK1/2 and CSE1L phosphorylation in A375 melanoma cells and HT-29 colorectal cancer cells. In the melanoma xenograft model, serum phospho-CSE1L level declined 5 days after vemurafenib/sunitinib treatment and 3 days after sorafenib/lapatinib treatment in the HT-29 colon cancer xenograft model. Vemurafenib/sunitinib and sorafenib/lapatinib treatments resulted in tumor regression. CONCLUSIONS: Our results indicated that serum phospho-CSE1L is useful for early detecting the efficacy of targeted therapy in initial treatment and for monitoring emerging secondary drug resistance to facilitate timely therapeutic decision making. BioMed Central 2015-06-13 /pmc/articles/PMC4467675/ /pubmed/26070816 http://dx.doi.org/10.1186/s12967-015-0553-6 Text en © Lee et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Lee, Woan-Ruoh Shen, Shing-Chuan Shih, Yi-Hsien Chou, Chia-Lun Tseng, Jonathan Te-Peng Chin, Szu-Ying Liu, Kao-Hui Chen, Yen-Chou Jiang, Ming-Chung Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts |
title | Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts |
title_full | Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts |
title_fullStr | Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts |
title_full_unstemmed | Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts |
title_short | Early decline in serum phospho-CSE1L levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts |
title_sort | early decline in serum phospho-cse1l levels in vemurafenib/sunitinib-treated melanoma and sorafenib/lapatinib-treated colorectal tumor xenografts |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467675/ https://www.ncbi.nlm.nih.gov/pubmed/26070816 http://dx.doi.org/10.1186/s12967-015-0553-6 |
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