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Phospho Akt mediates multidrug resistance of gastric cancer cells through regulation of P-gp, Bcl-2 and Bax.

2007; National Institutes of Health; Volume: 26; Issue: 2 Linguagem: Inglês

Zhicheng Han, Liu Hong, Ying Han, Kaichun Wu, Suji Han, Huanjun Shen, Cheng Li, Liping Yao, Tiankui Qiao, Daiming Fan,

Cancer therapeutics and mechanisms

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.