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Oncol Lett:Interference of P-REX2a may inhibit proliferation and reverse the resistance of SGC7901 cells to doxorubicin.

2018-08-30 10:20  来源:未知  编辑:高国雷   点击:
 
Ai Y1Zhou Q1Li L1Pan Z1Guo M1Han J2.

Author information

1
Department of Gastroenterology, The First People's Hospital of Yichang, China Three Georges University, Yichang, Hubei 443000, P.R. China.
2
Department of Anesthesiology, Ren He Hospital of Three Gorges University, Yichang, Hubei 443000, P.R. China.

Abstract

Drug resistance inhibits the efficacy of doxorubicin in gastric cancer. Phosphatidylinositol 3,4,5-trisphosphate RAC exchanger 2a (P-REX2a) activates the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway by binding to and inactivating phosphatase and tensin homolog (PTEN), which functions as a tumor promoter in a number of types of cancer. However, there is no research concerning the association between P-REX2a expression and drug resistance in gastric cancer. In the present study, the expression of P-REX2a in clinical gastric cancer tissues was detected, and the mechanism of doxorubicin resistance in the gastric cancer cell line SGC7901 was investigated. Using reverse transcription-quantitative polymerase chain reaction and western blotting, it was demonstrated that the mRNA and protein expression of P-REX2a was increased in gastric cancer tissues. MTT assays were also used to determine proliferation, and proliferation was revealed to be reduced following transfection of P-REX2a small interfering (si)RNA. When the cells were treated with 0.3 µM doxorubicin for 24 h, the rate of apoptosis in the siRNA-transfected groups significantly increased and no marked changes in of PTEN and Akt expression were observed. By contrast, the activity of PTEN increased, and the expression of p-Akt (S473) decreased in the P-REX2a siRNA-transfected group compared with the control. The detection of PTEN enzymatic activity in the present study was based on phosphatidylinositol-3,4,5-trisphosphate. Therefore, it was concluded that P-REX2a may participate in the generation of resistance to doxorubicin in gastric cancer, and this may be associated with the upregulation of the PI3K/Akt signaling pathway via inactivation of PTEN.

KEYWORDS:

doxorubicin; drug resistance; gastric cancer; phosphatidylinositol 3,4,5-trisphosphate RAC exchanger 2a; signal pathway


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