Constitutively Active Akt Contributes to Vincristine Resistance in Human Retinoblastoma Cells

ABSTRACT

Akt mediates survival signals which preserve various cancer cells from apoptosis. Its correlation with chemoresistance of cancer cells has attracted much attention. But how Akt affects vincristine-induced cell death in retinoblastoma is unknown. Here we show that Akt activity is involved in vincristine-induced cytotoxicity in retinoblastoma SO-Rb50 cells. Inhibition of Akt can decrease the survival of both sensitive and vincristine-resistant SO-Rb50 cells and increase the sensitivity of both cell lines to vincristine by enhancing the cell apoptosis and increasing the cellular accumulation of the drug. Akt may be a target for reducing drug resistance that improves the treatment for retinoblastoma.

Keywords: :

• Drug resistance
• Akt
• Vincristine
• P-glycoprotein
• Retinoblastoma

ACKNOWLEDGMENTS

The investigation was partly supported by National Natural Science Foundation of China (30772377, 2008) and was accomplished in Beijing Ophthalmology and Visual Sciences Key Lab, Capital Medical University School of Ophthalmology, Beijing, China. We sincerely appreciate the help granted by teacher Qing-jun Lu and Ke-gao Liu from the lab.