Abstract
Lung cancer is one of the leading causes of death in the world. The underlying cause for lung cancer has been attributed to various factors that include alteration and mutation in the tumor suppressor genes. Restoration of normal function of the tumor suppressor gene is a potential therapeutic strategy. Recent studies have identified a group of candidate tumor suppressor genes on human chromosome 3p21.3 that are frequently deleted in human lung and breast cancers. Among the various genes identified in the 3p21.3 region, we tested the antitumor activity of the FUS1 gene in two human non-small-cell lung cancer (NSCLC) xenografts in vivo. Intratumoral administration of FUS1 gene complexed to DOTAP:cholesterol (DOTAP:Chol) liposome into subcutaneous H1299 and A549 lung tumor xenograft resulted in significant (P=.02) inhibition of tumor growth. Furthermore, intravenous injections of DOTAP:Chol–FUS1 complex into mice bearing experimental A549 lung metastasis demonstrated significant (P=.001) decrease in the number of metastatic tumor nodules. Finally, lung tumor-bearing animals when treated with DOTAP:Chol–FUS1 complex demonstrate prolonged survival (median survival time: 80 days, P=.01) compared to control animals. This result demonstrates the potent tumor suppressive activity of the FUS1 gene and is a promising therapeutic agent for treatment of primary and disseminated human lung cancer.
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Acknowledgements
We thank Nora Rios for assistance in preparation of the manuscript. This work was supported in part by Public Health Service Grant P01 CA78778-01A1 (JAR), by the Specialized Program of Research Excellence (SPORE) in Lung Cancer 2P50-CA70970-04 (JDM and JAR); by a Career Development Award P50-CA70907-5 (RR); by gifts to the Division of Surgery, from Tenneco and Exxon for the Core Laboratory Facility; by the UT MD Anderson Cancer Center Support Core Grant CA 16672; by the Texas Tobacco Settlement Fund as appropriated by the Texas State Legislature (Project 8), by the MD Anderson WM Keck Center for Cancer Gene Therapy (JR, RR), by Texas Higher Education Coordinating Board ATP/ARP Grant 003657-0078-2001 (RR); by BESCT Lung Cancer Program grant DAMD17-01-1-0689 (LJ, RR); by TARGET Lung Cancer Grant DAMD17-02-1-0706 [LJ, RR]; by Cancer Center Support (CORE) Grant CA 16672; and by a sponsored research agreement with Introgen Therapeutics, Inc.
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Ito, I., Ji, L., Tanaka, F. et al. Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent antitumor activity against human lung cancer in vivo. Cancer Gene Ther 11, 733–739 (2004). https://doi.org/10.1038/sj.cgt.7700756
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DOI: https://doi.org/10.1038/sj.cgt.7700756