Phospho Akt mediates multidrug resistance of gastric cancer cells through regulation of P-gp, Bcl-2 and Bax.
Phosphatidylinositol 3-kinase/Akt pathway is an important intracellular pathway that is frequently activated in cancer cells. The role of P-AKT in multidrug resistance of gastric cancer cells and the possible underlying mechanisms are here investigated. Up-regulation of P-AKT expression could confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on AGS cells, and suppress adriamycin-induced apoptosis, along with decreased accumulation and increased releasing amount of adriamycin. P-AKT could significantly up-regulate the expression of Bcl-2, and down-regulate the expression of Bax, but not alter the expression of PTEN in gastric cancer cells. Inhibition of P-AKT expression could partially reverse P-AKT-mediated multidrug resistance and significantly up-regulate P53 expression, and down-regulate the expression of P-glycoprotein and the transcription of the multidrug resistance gene 1. Further studies of the biological functions of P-AKT may be helpful for understanding the mechanisms of multidrug resistance of gastric cancer and developing possible therapeutical strategies.
Han
Z
Z
State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Hong
L
L
Han
Y
Y
Wu
K
K
Han
S
S
Shen
H
H
Li
C
C
Yao
L
L
Qiao
T
T
Fan
D
D
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D018432:Drug Resistance, Multiple; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology*; D014158:Transcription, Genetic; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051057:Proto-Oncogene Proteins c-akt