The Effects of Lentivirus-mediated shRNA Interference Targeting Mcl-1 on Growth of NK/T-cell Lymphoma

Abstract

Myeloid leukemia-1 (Mcl-1) gene has been reported as an important factor in various types of cancer, but little research was processed on natural killer (NK)/T-cell lymphoma, a kind of a highly aggressive disease with a poor prognosis. Here we investigated the expression of Mcl-1 in seven lymphoma cell lines and its potential role as a molecular drug target for NK/T-cell lymphoma therapy by using lentivirus-mediated shRNA interference targeting Mcl-1 (lenti-shMcl-1). In our study, the expression of Mcl-1 in different lymphoma cell lines were evaluated firstly, after that lenti-shMcl-1 was constructed and transduced into NK/T-cell lymphoma cell line SNK-6 which had a high level expression of Mcl-1. Methylthiazolete-Trazolium (MTT) assay and flow cytometry (FCA) were employed to detect the status of proliferation and apoptosis after infection. Lastly we investigated the effects of chemotherapy agent vincristine (VCR) combination with lenti-shMcl-1 by MTT and FCA assay. The results showed that Mcl-1 gene expressed in all seven lymphoma cell lines at different levels. Recombinant lentiviruses could infect SNK-6 cells effectively. Mcl-1 expression level was remarkably down-regulated after infection with lenti-shMcl-1. The growth of SNK-6 cells was inhibited significantly through apoptosis pathway. Otherwise, lenti-shMcl-1 also revealed a significant chemosensitizing effect in combination with vincristine. In a word, we demonstrated that lenti-shMcl-1 had a significant anti-NK/T cell lymphoma effect and targeting Mcl-1 therapy could be a promising novel approach in treatment of lymphoma.