Induction of non-small cell lung carcinoma apoptosis using soluble RGD-TRAIL by targeting the integrin receptor of tumor cells

Yao,Ruyong; Sui,Aihua; Wang,Zhenli; Liu,Shihai; Zhou,Quan; Liu,Xiangping; Zhang,Haiping

doi:10.3892/mmr.2012.1071

December 2012 Volume 6 Issue 6

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December 2012 Volume 6 Issue 6

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Article

Induction of non-small cell lung carcinoma apoptosis using soluble RGD-TRAIL by targeting the integrin receptor of tumor cells

Authors:
- Ruyong Yao
- Aihua Sui
- Zhenli Wang
- Shihai Liu
- Quan Zhou
- Xiangping Liu
- Haiping Zhang
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Affiliations: Central Laboratory, Affiliated Hospital of Qingdao University, Medical College, Qingdao 266003, P.R. China, Department of Pharmacology, The First Sanatorium of Jinan Military District, Qingdao 266001, P.R. China, Department of Clinical Laboratory, Affiliated Hospital of Qingdao University, Medical College, Qingdao 266003, P.R. China
Pages: 1355-1360
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Published online on: September 10, 2012

https://doi.org/10.3892/mmr.2012.1071
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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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Induction of non-small cell lung carcinoma apoptosis using soluble RGD-TRAIL by targeting the integrin receptor of tumor cells

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