Induction of non-small cell lung carcinoma apoptosis using soluble RGD-TRAIL by targeting the integrin receptor of tumor cells
- Authors:
- Published online on: September 10, 2012 https://doi.org/10.3892/mmr.2012.1071
- Pages: 1355-1360
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Abstract
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics that exhibits the ability to preferentially induce apoptosis in malignant cells. RGD peptides bind to the integrins, ανβ3 and ανβ5, which are selectively expressed in tumor neovasculature and at the surface of certain tumor cells. To enhance the antitumor effect, an RGD-TRAIL protein, in which TRAIL was fused with the RGD motif-containing cell adhesive sequence, GRGDNP (gly-arg-gly-asp-asn-pro), was constructed and evaluated for bioactivity. The soluble TRAIL and RGD-TRAIL proteins were expressed in Escherichia coli BL21 (DE3) and purified using a non-denaturing method. The antitumor effect of the purified RGD-TRAIL on cell proliferation was evaluated in vitro using MTT and wound healing assays and cell apoptosis was assessed by Hoechst 33342 staining and PARP expression analysis. The results revealed that RGD-TRAIL inhibited the proliferation of multiple tumor cell lines (A549, NCI-H1299 and HCC827). Western blot analysis demonstrated that the treatment of tumor cells with RGD-TRAIL activated the apoptotic pathway by the cleavage of PARP, in the same way as wild-type TRAIL (wtTRAIL). These results demonstrate that RGD-TRAIL possesses more potent antitumor effects than wtTRAIL and, therefore, merits further investigation in preclinical and clinical studies.
