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BV6, an IAP antagonist, activates apoptosis and enhances radiosensitization of non-small cell lung carcinoma in vitro. J Thorac Oncol 2011 Nov;6(11):1801-9

Date

07/16/2011

Pubmed ID

21760551

Pubmed Central ID

PMC3196825

DOI

10.1097/JTO.0b013e318226b4a6

Abstract

INTRODUCTION: Defects in the apoptosis pathway limit the effectiveness of radiation in non-small cell lung cancer (NSCLC) therapy. BV6 is an antagonist of cIAP1 and XIAP, members of the inhibitors of apoptosis (IAP) family. We investigated the potential of BV6 to sensitize NSCLC cell lines to radiation.

METHODS: HCC193 and H460 lung cancer cell lines were treated with BV6 to investigate the effects of drug administration on cell proliferation, apoptosis, inhibition of XIAP and cIAP1, and radiosensitivity. Subsequent immunoblotting and Hoechst staining were used to determine the role of apoptosis in radiosensitization. Finally, the pathway of apoptosis was characterized by Western blot analysis for cleaved caspase-8 and cleaved caspase-9 and enzyme-linked immunosorbent assays for TNF-α.

RESULTS: HCC193 was found to be more sensitive than H460 to BV6-induced apoptosis in a concentration-dependent and time-dependent manner. BV6 significantly sensitized both cell lines to radiation (HCC193-DER = 1.38, p < 0.05 at 1 μM BV6; H460-DER = 1.42, p < 0.05 at 5 μM BV6), but a higher concentration of and longer incubation time with BV6 was necessary for H460 cells. The BV6-induced radiosensitization of HCC193 favored the extrinsic pathway of apoptosis, whereas that of H460 favored the intrinsic pathway.

CONCLUSIONS: BV6, an IAP antagonist, significantly enhanced the radiosensitization of HCC193 and H460 cells in vitro. More research is warranted to test the mechanism of action of BV6 and to assess its potential in vivo and in the clinical setting.

Author List

Li W, Li B, Giacalone NJ, Torossian A, Sun Y, Niu K, Lin-Tsai O, Lu B

Author

Yunguang Sun MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Apoptosis
Carcinoma, Non-Small-Cell Lung
Cesium Radioisotopes
Chemoradiotherapy
Enzyme Inhibitors
Enzyme-Linked Immunosorbent Assay
Humans
In Vitro Techniques
Inhibitor of Apoptosis Proteins
Lung Neoplasms
Radiation-Sensitizing Agents
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a