Journal
ONCOLOGY RESEARCH
Volume 23, Issue 3, Pages 129-136Publisher
COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096504015X14500513118029
Keywords
Gastric carcinoma (GC); Hypoxia-inducible factor-1 alpha; Drug resistance; Drug sensitivity test in vitro; Apoptosis-related genes
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In this study, the effects of hypoxia-inducible factor-1 alpha (HIF-1 alpha) on gastric carcinoma (GC) drug resistance through apoptosis-related genes are investigated. First, HIF-1 alpha-specific siRNA was synthetized and transfected into drug-resistant GC cell line OCUM-2MD3/L-OHP. Then MTT assay was applied to test the inhibition rate of GC cells by 5-fluorouracil (5-FU) and oxaliplatin (L-OHP). After that, flow cytometry (FCM) was applied to measure apoptosis rate. qPCR and Western blot assay were employed to detect HIF-1 alpha and apoptosis-related genes. Results showed that HIF-1 alpha in OCUM-2MD3/L-OHP cells was higher than that in OCUM-2MD3 and gastric epithelial cells. After HIF-1 alpha-siRNA transfection, inhibition rates of 5-FU and L-OHP to tumor cells increased significantly. FCM results showed that apoptosis rate of OCUM-2MD3/L-OHP cells increased significantly. After HIF-1 alpha-siRNA transfection, survivin and Bcl-2 decreased, whereas Box, caspase 3, and caspase 8 increased significantly. Results from this study seem to confirm that HIF-1 alpha getting involved in GC drug resistance is possibly due to its regulation of some apoptosis-related genes. HIF-1 alpha may be a potential target to reverse drug resistance of GC.
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