title: Phospho Akt mediates multidrug resistance of gastric cancer cells through regulation of P-gp, Bcl-2 and Bax.
abstract: 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.
authors.affiliation: State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Han
authors.forename: L
authors.initials: L
authors.lastname: Hong
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Han
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Yao
authors.forename: T
authors.initials: T
authors.lastname: Qiao
authors.forename: D
authors.initials: D
authors.lastname: Fan
mesh_terms: 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
chemical_list: 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