PI3K/Akt inhibition modulates multidrug resistance and activates NF-kB in murine lymphoma cell lines

GARCÍA MARIANA; ALANIZ LAURA; CORDÓ RUSSO ROSALÍA; ALVAREZ ELIDA; HAJOS SILVIA

LEUKEMIA RESEARCH

Elsevier

Lugar: Irlanda; Año: 2009 vol. 33 p. 288 - 296

0145-2126

Upregulation of the PI3K/Akt pathway has been described in some tumors related to multidrug resistance (MDR). The aim of this work was to analyze the relationship between PI3K/Akt, MDR and NF-kB in murine lymphoma cell lines resistant to vincristine (LBR-V160) and doxorubicin (LBR-D160) as well as in the sensitive line (LBR-). PI3K/Akt activity, analyzed by phosphatidylinositol trisphosphate production and phosphorylated Akt (p-Akt) expression, was higher in the resistant cell lines than in the sensitive one and inhibition with wortmannin or LY294002 improved apoptosis in the resistant cell lines.  Vincristine but not doxorubicin increased p-Akt expression whereas co-treatment with PI3K inhibitors and vincristine increased apoptosis in the three cell lines. Wortmannin and LY294002 inhibited P-glycoprotein function and also increased NF-kB activity. We concluded that the PI3K/Akt pathway is involved in MDR in lymphoma cell lines and PI3K/Akt inhibition correlates down-regulation of NF-kB activity and inhibition of Pgp function.