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.
Highlights
Gastric cancer is one of the most common malignant tumors in the world and the third leading cause of cancer-related death [1]
Our analysis provided new insights into the role of 5-FU in increasing sensitivity to Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). 5-FU can be used as a sensitizer for TRAIL, and its administration is a potential strategy for the treatment of gastric cancer
We investigated whether 5-FU treatment can sensitize gastric cancer cells to TRAIL-induced growth inhibition and apoptosis both in vitro and in vivo
Summary
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. Gastric cancer cells are usually insensitive to TRAIL so reducing this drug resistance may improve the treatment of gastric cancer
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