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Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway

There were approximately 1.93 million new cases and 940 000 deaths from colorectal cancer in 2020. The first‐line chemotherapeutic drugs for colorectal cancer are mainly based on 5‐fluorouracil, although the use of these drugs is limited by the development of drug resistance. Consequently, there is...

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Autores principales: Zhang, Wen, Sun, Ruiqian, Zhang, Yongjun, Hu, Rong, Li, Qian, Wu, Weili, Cao, Xinyu, Zhou, Jiajian, Pei, Jianfeng, Yuan, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564099/
https://www.ncbi.nlm.nih.gov/pubmed/34496154
http://dx.doi.org/10.1002/2211-5463.13290
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author Zhang, Wen
Sun, Ruiqian
Zhang, Yongjun
Hu, Rong
Li, Qian
Wu, Weili
Cao, Xinyu
Zhou, Jiajian
Pei, Jianfeng
Yuan, Ping
author_facet Zhang, Wen
Sun, Ruiqian
Zhang, Yongjun
Hu, Rong
Li, Qian
Wu, Weili
Cao, Xinyu
Zhou, Jiajian
Pei, Jianfeng
Yuan, Ping
author_sort Zhang, Wen
collection PubMed
description There were approximately 1.93 million new cases and 940 000 deaths from colorectal cancer in 2020. The first‐line chemotherapeutic drugs for colorectal cancer are mainly based on 5‐fluorouracil, although the use of these drugs is limited by the development of drug resistance. Consequently, there is a need for novel chemotherapeutic drugs for the efficient treatment of colorectal cancer patients. In the present study, we screened 160 drugs approved by the Food and Drug Administration and identified that cabazitaxel (CBT), a microtube inhibitor, can suppress colony formation and cell migration of colorectal cancer cells in vitro. CBT also induces G2/M phase arrest and apoptosis of colorectal cancer cells. Most importantly, it inhibits the growth of colorectal cancer cell xenograft tumors in vivo. Transcriptome analysis by RNA‐sequencing revealed that Tub family genes are abnormally expressed in CBT‐treated colorectal cancer cells. The expression of several p53 downstream genes that are associated with cell cycle arrest, apoptosis, and inhibition of angiogenesis and metastasis is induced by CBT in colorectal cancer cells. Overall, our results suggests that CBT suppresses colorectal cancer by upregulating the p53 pathway, and thus CBT may have potential as an alternative chemotherapeutic drug for colorectal cancer.
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spelling pubmed-85640992021-11-09 Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway Zhang, Wen Sun, Ruiqian Zhang, Yongjun Hu, Rong Li, Qian Wu, Weili Cao, Xinyu Zhou, Jiajian Pei, Jianfeng Yuan, Ping FEBS Open Bio Research Articles There were approximately 1.93 million new cases and 940 000 deaths from colorectal cancer in 2020. The first‐line chemotherapeutic drugs for colorectal cancer are mainly based on 5‐fluorouracil, although the use of these drugs is limited by the development of drug resistance. Consequently, there is a need for novel chemotherapeutic drugs for the efficient treatment of colorectal cancer patients. In the present study, we screened 160 drugs approved by the Food and Drug Administration and identified that cabazitaxel (CBT), a microtube inhibitor, can suppress colony formation and cell migration of colorectal cancer cells in vitro. CBT also induces G2/M phase arrest and apoptosis of colorectal cancer cells. Most importantly, it inhibits the growth of colorectal cancer cell xenograft tumors in vivo. Transcriptome analysis by RNA‐sequencing revealed that Tub family genes are abnormally expressed in CBT‐treated colorectal cancer cells. The expression of several p53 downstream genes that are associated with cell cycle arrest, apoptosis, and inhibition of angiogenesis and metastasis is induced by CBT in colorectal cancer cells. Overall, our results suggests that CBT suppresses colorectal cancer by upregulating the p53 pathway, and thus CBT may have potential as an alternative chemotherapeutic drug for colorectal cancer. John Wiley and Sons Inc. 2021-10-11 /pmc/articles/PMC8564099/ /pubmed/34496154 http://dx.doi.org/10.1002/2211-5463.13290 Text en © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Zhang, Wen
Sun, Ruiqian
Zhang, Yongjun
Hu, Rong
Li, Qian
Wu, Weili
Cao, Xinyu
Zhou, Jiajian
Pei, Jianfeng
Yuan, Ping
Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway
title Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway
title_full Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway
title_fullStr Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway
title_full_unstemmed Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway
title_short Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway
title_sort cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564099/
https://www.ncbi.nlm.nih.gov/pubmed/34496154
http://dx.doi.org/10.1002/2211-5463.13290
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