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...

Full description

Saved in:
Bibliographic Details
Main Authors: Wen Zhang, Ruiqian Sun, Yongjun Zhang, Rong Hu, Qian Li, Weili Wu, Xinyu Cao, Jiajian Zhou, Jianfeng Pei, Ping Yuan
Format: Article
Language:English
Published: Wiley 2021-11-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.13290
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849322400109297664
author Wen Zhang
Ruiqian Sun
Yongjun Zhang
Rong Hu
Qian Li
Weili Wu
Xinyu Cao
Jiajian Zhou
Jianfeng Pei
Ping Yuan
author_facet Wen Zhang
Ruiqian Sun
Yongjun Zhang
Rong Hu
Qian Li
Weili Wu
Xinyu Cao
Jiajian Zhou
Jianfeng Pei
Ping Yuan
author_sort Wen Zhang
collection DOAJ
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.
format Article
id doaj-art-ddfa0a02de124e0fac023bd8880ae5e5
institution Kabale University
issn 2211-5463
language English
publishDate 2021-11-01
publisher Wiley
record_format Article
series FEBS Open Bio
spelling doaj-art-ddfa0a02de124e0fac023bd8880ae5e52025-08-20T03:49:22ZengWileyFEBS Open Bio2211-54632021-11-0111113032305010.1002/2211-5463.13290Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathwayWen Zhang0Ruiqian Sun1Yongjun Zhang2Rong Hu3Qian Li4Weili Wu5Xinyu Cao6Jiajian Zhou7Jianfeng Pei8Ping Yuan9Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaGuangdong Country Garden School Foshan City ChinaDermatology Hospital Southern Medical University Guangzhou ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaInstitute of Clinical Medical Sciences,, Center of Respiratory Medicine China‐Japan Friendship Hospital Beijing ChinaDermatology Hospital Southern Medical University Guangzhou ChinaCenter for Quantitative Biology,, Academy for Advanced Interdisciplinary Studies Peking University Beijing ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaThere 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.https://doi.org/10.1002/2211-5463.13290cabazitaxelcolorectal cancer cellHCT116RNA‐sequencingxenograft
spellingShingle Wen Zhang
Ruiqian Sun
Yongjun Zhang
Rong Hu
Qian Li
Weili Wu
Xinyu Cao
Jiajian Zhou
Jianfeng Pei
Ping Yuan
Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway
FEBS Open Bio
cabazitaxel
colorectal cancer cell
HCT116
RNA‐sequencing
xenograft
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 cabazitaxel
colorectal cancer cell
HCT116
RNA‐sequencing
xenograft
url https://doi.org/10.1002/2211-5463.13290
work_keys_str_mv AT wenzhang cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT ruiqiansun cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT yongjunzhang cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT ronghu cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT qianli cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT weiliwu cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT xinyucao cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT jiajianzhou cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT jianfengpei cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway
AT pingyuan cabazitaxelsuppressescolorectalcancercellgrowthviaenhancingthep53antitumorpathway