ScholarLens Back to search
2009•Di-san junyi daxue xuebaoRequires access

Suppressing PI3K/PKB signal pathway to reverse drug resistance of gastric carcinoma cell line SGC7901/VCR:efficiency and mechanism

Yanli Wang

Open publisher page 0 citations

Abstract

Objective To investigate the reversing effects on drug resistance of gastric carcinoma by suppressing PI3K/PKB signal pathway,and explore its implicated mechanism.Methods MTT assay was used to test the inhibitory effects of VCR alone or VCR in combination with PI3K/PKB inhibitor,LY294002 on SGC7901/VCR cells.The SGC7901 treated with or without LY294002 served as control.The protein levels of PKB and phospho-PKB in the above VCR cells were determined by Western blot analysis.The mRNA expressions of MDR1,Bax and Bcl-2 were evaluated by semi-quantitative PCR with β-actin as the inner control.The apoptosis was detected by flow cytometry.Tumor volume on the tumor-bearing mice transplanted by SGC7901/VCR cells or cells treated by VCR,LY294002 and their combination respectively was measure for the in vivo effect of LY294002.Results LY294002 enhanced the sensitivities of SGC7901/VCR cells to VCR significantly,and promoted the apoptosis rate induced by VCR prominently,with their corresponding drug resistant index decreasing from 40.45 to 8.50.The protein level of phospho-PKB was reduced,and the mRNA expression levels of MDR1 and Bcl-2 were inhibited(P0.01),while that of Bax was improved significantly(P0.01).LY294002 improved the growth inhibitory effect of VCR on transplanted gastric carcinoma in nude mice.Conclusion Suppressing PI3K/PKB signal pathway by LY294002 reverses the drug resistance of gastric carcinoma cell line SGC7901/VCR.Reduction of MDR1 expression levels,and regulation of apoptosis-related genes,such as Bax and Bcl-2 may play key roles in this progress.

About this research paper

What this paper is about

Objective To investigate the reversing effects on drug resistance of gastric carcinoma by suppressing PI3K/PKB signal pathway,and explore its implicated mechanism.Methods MTT assay was used to test the inhibitory effects of VCR alone or VCR in combination with PI3K/PKB inhibitor,LY294002 on SGC7901/VCR cells.The SGC7901 treated with or without LY294002 served as control.The protein levels of PKB and phospho-PKB in the above VCR cells were determined by Western blot analysis.The mRNA expressions of MDR1,Bax and Bcl-2 were evaluated by semi-quantitative PCR with β-actin as the inner control.The apoptosis was detected by flow cytometry.Tumor volume on the tumor-bearing mice transplanted by SGC7901/VCR cells or cells treated by VCR,LY294002 and their combination respectively was measure for the in vivo effect of LY294002.Results LY294002 enhanced the sensitivities of SGC7901/VCR cells to VCR significantly,and promoted the apoptosis rate induced by VCR prominently,with their corresponding drug resistant index decreasing from 40.45 to 8.50.The protein level of phospho-PKB was reduced,and the mRNA expression levels of MDR1 and Bcl-2 were inhibited(P0.01),while that of Bax was improved significantly(P0.01).LY294002 improved the growth inhibitory effect of VCR on transplanted gastric carcinoma in nude mice.Conclusion Suppressing PI3K/PKB signal pathway by LY294002 reverses the drug resistance of gastric carcinoma cell line SGC7901/VCR.Reduction of MDR1 expression levels,and regulation of apoptosis-related genes,such as Bax and Bcl-2 may play key roles in this progress.

Why it matters

A significance statement is not available in the OpenAlex record.

Key contribution

A contribution statement is not available in the OpenAlex record.

Method / approach

Method details are not available in the OpenAlex metadata.

Main findings

Findings are not separately available in the OpenAlex metadata.

Limitations

Limitations are not available in the OpenAlex metadata.

Applications

Application details are not available in the OpenAlex metadata.

Available abstract

Objective To investigate the reversing effects on drug resistance of gastric carcinoma by suppressing PI3K/PKB signal pathway,and explore its implicated mechanism.Methods MTT assay was used to test the inhibitory effects of VCR alone or VCR in combination with PI3K/PKB inhibitor,LY294002 on SGC7901/VCR cells.The SGC7901 treated with or without LY294002 served as control.The protein levels of PKB and phospho-PKB in the above VCR cells were determined by Western blot analysis.The mRNA expressions of MDR1,Bax and Bcl-2 were evaluated by semi-quantitative PCR with β-actin as the inner control.The apoptosis was detected by flow cytometry.Tumor volume on the tumor-bearing mice transplanted by SGC7901/VCR cells or cells treated by VCR,LY294002 and their combination respectively was measure for the in vivo effect of LY294002.Results LY294002 enhanced the sensitivities of SGC7901/VCR cells to VCR significantly,and promoted the apoptosis rate induced by VCR prominently,with their corresponding drug resistant index decreasing from 40.45 to 8.50.The protein level of phospho-PKB was reduced,and the mRNA expression levels of MDR1 and Bcl-2 were inhibited(P0.01),while that of Bax was improved significantly(P0.01).LY294002 improved the growth inhibitory effect of VCR on transplanted gastric carcinoma in nude mice.Conclusion Suppressing PI3K/PKB signal pathway by LY294002 reverses the drug resistance of gastric carcinoma cell line SGC7901/VCR.Reduction of MDR1 expression levels,and regulation of apoptosis-related genes,such as Bax and Bcl-2 may play key roles in this progress.

Key concepts: PI3K/AKT/mTOR pathway, LY294002, Apoptosis, Protein kinase B, Cell culture, In vivo, Flow cytometry, MTT assay

Related papers

Related paper 1Related paper 2Related paper 3
Back to paper searchBrowse research topicsOriginal source
Suppressing PI3K/PKB signal pathway to reverse drug resistance of gastric carcinoma cell line SGC7901/VCR:efficiency and mechanism — Research Paper | ScholarLens