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Induction of non-small cell lung carcinoma apoptosis using soluble RGD-TRAIL by targeting the integrin receptor of tumor cells
- Source :
- Molecular Medicine Reports. 6:1355-1360
- Publication Year :
- 2012
- Publisher :
- Spandidos Publications, 2012.
-
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.
- Subjects :
- Cancer Research
Lung Neoplasms
CD30
Cell Survival
Recombinant Fusion Proteins
Cell
Antineoplastic Agents
Apoptosis
Biology
Biochemistry
TNF-Related Apoptosis-Inducing Ligand
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Escherichia coli
Genetics
medicine
Humans
Receptors, Vitronectin
Molecular Biology
Oncogene
Cell growth
Cell cycle
Integrin alphaVbeta3
medicine.anatomical_structure
Oncology
Cell culture
Cancer research
Molecular Medicine
Tumor necrosis factor alpha
Poly(ADP-ribose) Polymerases
Oligopeptides
A431 cells
Subjects
Details
- ISSN :
- 17913004 and 17912997
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Molecular Medicine Reports
- Accession number :
- edsair.doi.dedup.....9036b1134187d54725a5189e76629438