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

Abstract

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.

• Authors: Wen Zhang, Ruiqian Sun, Yongjun Zhang, Rong Hu, Qian Li, Weili Wu, Xinyu Cao, Jiajian Zhou, Jianfeng Pei, Ping Yuan
• Journal: FEBS open bio (FEBS Open Bio) Vol. 11 Issue 11 Pg. 3032-3050 (11 2021) ISSN: 2211-5463 [Electronic] England
• PMID: 34496154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Chemical References

• Taxoids
• Tumor Suppressor Protein p53
• cabazitaxel
• Fluorouracil

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism)
• Drug Screening Assays, Antitumor (methods)
• Fluorouracil (pharmacology)
• HCT116 Cells
• Humans
• Mice
• Taxoids (pharmacology)
• Tumor Suppressor Protein p53 (drug effects, metabolism)
• Xenograft Model Antitumor Assays