Synergistic effects of co-expression plasmid‑based ADAM10-specific siRNA and GRIM-19 on hepatocellular carcinoma in vitro and in vivo.

Abstract

A disintegrin and metalloproteinase 10 (ADAM10) has been demonstrated to correlate with hepatocellular carcinoma (HCC) grade and clinical outcome and its potential as a target for HCC therapy has been established. Gene associated with retinoid-interferon-induced mortality 19 (GRIM-19), a signal transducer and activator of transcription 3 (Stat3)-inhibitory protein, was identified as a potential tumor suppressor associated with growth inhibition and cell apoptosis. In the present study, we investigated whether a combined treatment with ADAM10-specific siRNA and GRIM19 gene could have an enhanced anticancer effectiveness on HCC in vitro and in vivo. We developed a dual expression plasmid that co-expressed ADAM10-specific siRNA and GRIM19, to evaluate its effects on HCC growth. Our results showed that simultaneous expression of ADAM10-specific siRNA and GRIM19 (pSi-ADAM10-GRIM19) in HepG2 cancer cells significantly inhibited the proliferation, migration and invasion, and induced cell apoptosis in vitro, and it also suppressed tumor growth in a nude mouse model when compared to the controls, either ADAM10-specific siRNA or GRIM-19 alone. In summary, our data demonstrated that a combined strategy of co-expressed ADAM10-specific siRNA and GRIM19 synergistically and more effectively suppressed HCC tumor growth, and has therapeutic potential for the treatment of HCC.