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Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells

In this study, the effects of hypoxia-inducible factor-1α (HIF-1α) on gastric carcinoma (GC) drug resistance through apoptosis-related genes are investigated. First, HIF-1α-specific siRNA was synthetized and transfected into drug-resistant GC cell line OCUM-2MD3/L-OHP. Then MTT assay was applied to...

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Autores principales: Zhao, Qun, Tan, Bi-Bo, Li, Yong, Fan, Li-Qiao, Yang, Pei-Gang, Tian, Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838699/
https://www.ncbi.nlm.nih.gov/pubmed/26931435
http://dx.doi.org/10.3727/096504015X14500513118029
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author Zhao, Qun
Tan, Bi-Bo
Li, Yong
Fan, Li-Qiao
Yang, Pei-Gang
Tian, Yuan
author_facet Zhao, Qun
Tan, Bi-Bo
Li, Yong
Fan, Li-Qiao
Yang, Pei-Gang
Tian, Yuan
author_sort Zhao, Qun
collection PubMed
description In this study, the effects of hypoxia-inducible factor-1α (HIF-1α) on gastric carcinoma (GC) drug resistance through apoptosis-related genes are investigated. First, HIF-1α-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-1α and apoptosis-related genes. Results showed that HIF-1α in OCUM-2MD3/L-OHP cells was higher than that in OCUM-2MD3 and gastric epithelial cells. After HIF-1α-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-1α-siRNA transfection, survivin and Bcl-2 decreased, whereas Bax, caspase 3, and caspase 8 increased significantly. Results from this study seem to confirm that HIF-1α getting involved in GC drug resistance is possibly due to its regulation of some apoptosis-related genes. HIF-1α may be a potential target to reverse drug resistance of GC.
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spelling pubmed-78386992021-02-16 Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells Zhao, Qun Tan, Bi-Bo Li, Yong Fan, Li-Qiao Yang, Pei-Gang Tian, Yuan Oncol Res Article In this study, the effects of hypoxia-inducible factor-1α (HIF-1α) on gastric carcinoma (GC) drug resistance through apoptosis-related genes are investigated. First, HIF-1α-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-1α and apoptosis-related genes. Results showed that HIF-1α in OCUM-2MD3/L-OHP cells was higher than that in OCUM-2MD3 and gastric epithelial cells. After HIF-1α-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-1α-siRNA transfection, survivin and Bcl-2 decreased, whereas Bax, caspase 3, and caspase 8 increased significantly. Results from this study seem to confirm that HIF-1α getting involved in GC drug resistance is possibly due to its regulation of some apoptosis-related genes. HIF-1α may be a potential target to reverse drug resistance of GC. Cognizant Communication Corporation 2016-02-29 /pmc/articles/PMC7838699/ /pubmed/26931435 http://dx.doi.org/10.3727/096504015X14500513118029 Text en Copyright © 2016 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Zhao, Qun
Tan, Bi-Bo
Li, Yong
Fan, Li-Qiao
Yang, Pei-Gang
Tian, Yuan
Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells
title Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells
title_full Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells
title_fullStr Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells
title_full_unstemmed Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells
title_short Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells
title_sort enhancement of drug sensitivity by knockdown of hif-1α in gastric carcinoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838699/
https://www.ncbi.nlm.nih.gov/pubmed/26931435
http://dx.doi.org/10.3727/096504015X14500513118029
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