Lentiviral vector-mediated upregulation of let-7a inhibits gastric carcinoma cell growth in vitro and in vivo.

OBJECTIVE: Let-7a, a molecule that is reduced in various cancers, has been associated with cell growth and proliferation. Upregulation of let-7a may inhibit tumor cell growth. To verify this hypothesis, let-7a gene overexpression was studied in gastric cancer cells in vitro and in vivo.

MATERIAL AND METHODS: A lentiviral system harboring both enhanced green fluorescent protein reporter gene and the let-7a short hairpin RNA expression cassette was firstly constructed. Then the stable let-7a gene overexpression SGC-7901 cells were established and real-time RT-PCR analysis was used to evaluate the expression of the let-7a gene. Their growth-inhibiting, cell cycle arrest characteristics were identified.

RESULTS: In SGC-7901/let-7a cells, let-7a expression was significantly increased. Their proliferation was obviously retarded and the cell cycle changed with increased G0/G1 arrest and decreased S phase. In animal experiments, SGC-7901/let-7a cell xenografts demonstrated growth suppression compared to parental or control gastric cancer cell xenografts.

CONCLUSION: The results demonstrated that lentiviral vector was capable of upregulating let-7a, resulting in impressive anticancer effects. It offers a powerful new strategy for the development of novel therapeutic interventions to treat human gastric carcinomas.