Asset Details
Do you wish to reserve the book?
ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting repair of DNA damage
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting repair of DNA damage
Do you wish to request the book?
ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting repair of DNA damage
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5-fluorouracil by inhibiting repair of DNA damage
2022
Overview
The repair of DNA damage caused by chemotherapy in cancer cells occurs mainly at two cell cycle checkpoints (G1 and G2) and is a factor contributing to chemoresistance. Most colorectal cancers harbor mutations in p53, the main pathway involved in the G1 checkpoint, and thus, are particularly dependent on the G2 checkpoint for DNA repair. The present study examined the effect of AZD6738, a specific inhibitor of ataxia telangiectasia mutated and rad3-related (ATR) involved in the G2 checkpoint, combined with 5-fluorouracil (5-FU), a central chemotherapeutic agent, on colorectal cancer cells. Since 5-FU has a DNA-damaging effect, its combination with AZD6738 is likely to enhance the therapeutic effect. The effects of the AZD6738/5-FU combination were evaluated in various colorectal cancer cells (HT29, SW480, HCT116 and DLD-1 cells) by flow cytometry (HT29 cells), western blotting (HT29 cells) and water-soluble tetrazolium 1 assays (HT29, SW480, HCT116 and DLD-1 cells), as well as in an experimental animal model (HT29 cells). In vitro, the AZD6738/5-FU combination increased the number of mitotic cells according to flow cytometry, decreased the checkpoint kinase 1 phosphorylation levels and increased cleaved caspase-3 and phosphorylated form of H2A.X variant histone levels according to western blotting, and decreased the proliferation rate of four colon cancer cell lines according to cell viability experiments. In vivo, xenografted colorectal cancer cells treated with the AZD6738/5-FU combination exhibited a marked decrease in proliferation compared with the 5-FU alone group. The present results suggested that AZD6738 enhanced the effect of 5-FU in p53-mutated colorectal cancer.
Publisher
D.A. Spandidos,Spandidos Publications,Spandidos Publications UK Ltd
Subject
/ Analysis
/ Animals
/ ataxia telangiectasia mutated and rad3-related inhibitor
/ Ataxia Telangiectasia Mutated Proteins - metabolism
/ AZD6738
/ Cancer
/ Colonic Neoplasms - genetics
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - genetics
/ DNA
/ Humans
/ Indoles
/ Kinases
/ Proteins
/ Reagents
