Apoptin-modified human mesenchymal stem cells inhibit growth of lung carcinoma in nude mice

Human mesenchymal stem cells (MSCs) represent a novel carrier for gene therapy and apoptin is a potential tumor-selective apoptosis-inducing protein. In the present study, the anti-tumoral effect of MSCs modified with apoptin against lung carcinoma was evaluated. Apoptin protein was expressed in a prokaryotic expression system and purified by affinity chromatography. Subsequently, anti-apoptin antibody was prepared by immunizing BALB/c mice with purified apoptin protein. Human MSCs were isolated, amplified and transduced with lentiviral vectors encoding full-length apoptin, in which the secretory signal and protein transduction sequence were added into the amino terminus to assist apoptin in entering into target cells. The differentiation and apoptin expression of apoptin-modified MSCs were confirmed. Subsequently, the anti-tumor effect of apoptin-modified MSCs was measured in vitro and in vivo. Following modification with apoptin, MSCs retained their differentiation capacity, and successfully synthesized and secreted apoptin, which entered target cells and selectively induced lung cancer cell apoptosis through activating caspase-3. The percentage of tumor cells with activated caspase-3 in the apoptin-modified MSCs group was markedly higher than that in the MSCs group (16.5±2.9% at 24 h and 27.3±2.0% at 48 h vs. 3.4±1.1% at 24 h and 2.2±0.6% at 48 h). When injected into nude mice, apoptin-modified MSCs inhibited the growth of lung carcinoma compared with that in the control groups (0.14±0.02 g vs. 0.21±0.04 g vs. 0.31±0.05 g, P<0.05). The results of the present study provided preclinical support of apoptin-based cancer therapy with MSCs as cellular vehicles.