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Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer

INTRODUCTION: Although the survival rate of colorectal cancer (CRC) patients can be improved by surgery, radiotherapy, and chemotherapy, the resistance to 5-fluorouracil (5-Fu) affects the effect of chemotherapy and the prognosis of patients. An increasing number of studies showed that 5-Fu resistan...

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Autores principales: Zhu, Yiping, Li, Kai, Zhang, Jieling, Wang, Lu, Sheng, Lili, Yan, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649235/
https://www.ncbi.nlm.nih.gov/pubmed/33177877
http://dx.doi.org/10.2147/CMAR.S255895
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author Zhu, Yiping
Li, Kai
Zhang, Jieling
Wang, Lu
Sheng, Lili
Yan, Liang
author_facet Zhu, Yiping
Li, Kai
Zhang, Jieling
Wang, Lu
Sheng, Lili
Yan, Liang
author_sort Zhu, Yiping
collection PubMed
description INTRODUCTION: Although the survival rate of colorectal cancer (CRC) patients can be improved by surgery, radiotherapy, and chemotherapy, the resistance to 5-fluorouracil (5-Fu) affects the effect of chemotherapy and the prognosis of patients. An increasing number of studies showed that 5-Fu resistance was the main reason for the failure of colorectal cancer treatment. The poor prognosis of colorectal cancer greatly harms people’s health. This study aimed to clarify the correlation between cyclin-dependent kinase 1 (CDK1) and 5-Fu-induced tumor resistance. MATERIALS AND METHODS: Cell proliferation and invasion experiments showed that down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation. The expression level of CDK1 was detected in 5-Fu-resistant CRC cells in vitro. Tumor growth was inhibited by down-regulation of CDK1 in tumor xenograft mouse models. RESULTS: We found that CDK1 was highly expressed in tumor tissues, especially in fluorouracil-resistant tissues. We also confirmed that the differential expression of 5-Fu in tumor tissues was related to tumor site, lymph node metastasis and stage. CDK1 promoted migration, invasion and inhibited apoptosis in 5-Fu-resistant CRC cells. Down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation and tumorigenesis in vivo. CONCLUSION: High expression of CDK1 may lead to poor clinical prognosis, and inhibition of CDK1 enhances 5-Fu sensitivity in CRC. Our research suggested that CDK1 may be used to predict 5-Fu efficacy and as a therapeutic target for CRC.
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spelling pubmed-76492352020-11-10 Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer Zhu, Yiping Li, Kai Zhang, Jieling Wang, Lu Sheng, Lili Yan, Liang Cancer Manag Res Original Research INTRODUCTION: Although the survival rate of colorectal cancer (CRC) patients can be improved by surgery, radiotherapy, and chemotherapy, the resistance to 5-fluorouracil (5-Fu) affects the effect of chemotherapy and the prognosis of patients. An increasing number of studies showed that 5-Fu resistance was the main reason for the failure of colorectal cancer treatment. The poor prognosis of colorectal cancer greatly harms people’s health. This study aimed to clarify the correlation between cyclin-dependent kinase 1 (CDK1) and 5-Fu-induced tumor resistance. MATERIALS AND METHODS: Cell proliferation and invasion experiments showed that down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation. The expression level of CDK1 was detected in 5-Fu-resistant CRC cells in vitro. Tumor growth was inhibited by down-regulation of CDK1 in tumor xenograft mouse models. RESULTS: We found that CDK1 was highly expressed in tumor tissues, especially in fluorouracil-resistant tissues. We also confirmed that the differential expression of 5-Fu in tumor tissues was related to tumor site, lymph node metastasis and stage. CDK1 promoted migration, invasion and inhibited apoptosis in 5-Fu-resistant CRC cells. Down-regulation of CDK1 inhibited fluorouracil-resistant CRC cell proliferation and tumorigenesis in vivo. CONCLUSION: High expression of CDK1 may lead to poor clinical prognosis, and inhibition of CDK1 enhances 5-Fu sensitivity in CRC. Our research suggested that CDK1 may be used to predict 5-Fu efficacy and as a therapeutic target for CRC. Dove 2020-11-04 /pmc/articles/PMC7649235/ /pubmed/33177877 http://dx.doi.org/10.2147/CMAR.S255895 Text en © 2020 Zhu et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhu, Yiping
Li, Kai
Zhang, Jieling
Wang, Lu
Sheng, Lili
Yan, Liang
Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer
title Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer
title_full Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer
title_fullStr Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer
title_full_unstemmed Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer
title_short Inhibition of CDK1 Reverses the Resistance of 5-Fu in Colorectal Cancer
title_sort inhibition of cdk1 reverses the resistance of 5-fu in colorectal cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649235/
https://www.ncbi.nlm.nih.gov/pubmed/33177877
http://dx.doi.org/10.2147/CMAR.S255895
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