sATP-binding cassette subfamily G member 2 enhances the multidrug resistance properties of human nasal natural killer/T cell lymphoma side population cells

Abstract

Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKL) is a rare type of non-Hodgkin's lymphoma that is associated with limited effective treatment options and unfavorable survival rate, which is partly the result of multidrug resistance (MDR). The presence of side population (SP) cells-SNK-6/ADM-SP (SSP) cells has been previously used to explore mechanisms of drug resistance. ATP-binding cassette subfamily G member 2 (ABCG2) is a gene involved in MDR and is closely associated with SPs. However, the function of ABCG2 in SSP cells is unclear. The present study verified the high expression of ABCG2 in SSP cells. The IC50 values of doxorubicin, cytarabine, cisplatin, gemcitabine and l-asparaginase were tested to evaluate drug sensitivity in SSP cells with different levels of ABCG2 expression. ABCG2 was identified as a gene promoting in MDR. ABCG2 upregulated cell proliferation, increased clonogenicity, increased invasive ability and decreased apoptosis, in vivo and in vitro, when cells were treated with gemcitabine. To conclude, ABCG2 enhanced MDR and increased the typical biological characteristics associated with cancer cells in SP cells. With further investigation of the ABCG2 gene could have the potential to reverse MDR in ENKL.