Abstract:
:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has the ability to selectively trigger cancer cell apoptosis and can be used as a target for tumor therapy. However, gastric cancer cells are usually insensitive to TRAIL so reducing this drug resistance may improve the treatment of gastric cancer. In this study, we used Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) experiments to determine the effects of 5-fluorouracil (5-FU) and TRAIL on the proliferation of gastric cancer cells. An Annexin V/propidium iodide (PI) staining experiment was used to detect apoptosis, and Western blotting was used to analyze the expression levels of apoptosis-related proteins and mitogen-activated protein kinase (MAPK) pathway proteins. The antitumor effects of 5-FU and TRAIL were verified in vivo using a nude mouse tumorigenesis experiment, and a TUNEL assay was performed to evaluate apoptosis in tumor tissue from the nude mice. We found the combination of 5-FU and TRAIL had a greater inhibitory effect on the proliferation of gastric cancer cells than 5-FU or TRAIL alone both in vivo and in vitro. 5-FU enhanced TRAIL-induced gastric cancer cell apoptosis by inactivating the MAPK pathway. Overall, our analysis firstly provided new insights into the role of 5-FU in increasing sensitivity to TRAIL. 5-FU can be used as a sensitizer for TRAIL, and its administration is a potential strategy for the treatment of gastric cancer.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Li H,Lv J,Guo J,Wang S,Liu S,Ma Y,Liang Z,Wang Y,Qi W,Qiu Wdoi
10.1016/j.bbrc.2021.01.006subject
Has Abstractpub_date
2021-01-18 00:00:00pages
108-115eissn
0006-291Xissn
1090-2104pii
S0006-291X(21)00028-0journal_volume
540pub_type
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