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

✍ Scribed by Mariana G. García; Laura D. Alaniz; Rosalía I. Cordo Russo; Elida Alvarez; Silvia E. Hajos

• Publisher: Elsevier Science
• Year: 2009
• Tongue: English
• Weight: 825 KB
• Volume: 33
• Category: Article
• ISSN: 0145-2126
• DOI: 10.1016/j.leukres.2008.06.010

✦ Synopsis

Upregulation of the phosphatidylinositol 3-kinase (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-kappaB 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 (Pgp) function and also increased NF-kappaB 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-kappaB activity and inhibition Pgp function.