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Tumor-Suppressive Effects of MBP-1 in Non–Small Cell Lung Cancer Cells

¹ Department of Pathology and ² Cancer Center, Saint Louis University, St. Louis, Missouri

Requests for reprints: Ratna B. Ray, Department of Pathology, Saint Louis University, 1402 South Grand Boulevard, St. Louis, MO 63104. Phone: 314-577-8331; Fax: 314-771-3816; E-mail: rayrb{at}slu.edu.

Lung cancer is the leading cause of cancer death among both men and women. Only 15% of people diagnosed with non–small cell lung cancer (NSCLC) survive this disease beyond 5 years. Thus, novel therapeutic strategies are urgently needed to improve the clinical management of this devastating disease. We have previously shown the antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of non–small cell lung tumor growth. We have observed that exogenous expression of MBP-1 in NSCLC cells (H1299) induces massive cell death. To determine the gene therapeutic potential of MBP-1, replication-deficient recombinant adenovirus expressing MBP-1 was given intratumorally in human lung cancer xenografts in nude mice. Our results showed a significant regression of lung tumor growth and prolonged survival on treatment with MBP-1 compared with the control groups (saline or dl312). Subsequently, the mechanism of MBP-1–mediated H1299 cell death was investigated. Our results suggested that MBP-1 induced poly(ADP-ribose) polymerase cleavage in H1299 cells; however, treatment with pan-caspase inhibitor did not protect against MBP-1–induced cell death. Cells transduced with MBP-1 displayed early plasma membrane permeability, mitochondrial damage without cytochrome c release, and extensive cytoplasmic vacuolation, yielding a morphotype that is typical of necrosis. Taken together, this study suggests that MBP-1 expression induces a novel form of necrosis-like cell death and MBP-1 could be a potential gene therapeutic candidate against non–small cell lung tumor growth. (Cancer Res 2006; 66(24): 11907-12)

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