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Journal of the Society for Gynecologic Investigation
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A Bcl-xS Adenovirus Demonstrates Therapeutic Efficacy in an Ascites Model of Human Breast Cancer

Venil N. Sumantran, PhD

David S. Lee, BS

Vicki V. Baker, MD

Susan Murray, MS,ScD

Myla Strawderman, MS

Department of Internal Medicine and Comprehensive Cancer Center, Cancer and Geriatrics Center, the Department of Obstetrics and Gynecology, Department of Biostatistics, School of Public Health, and Biostatistics Core, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan

Max S. Wicha, MD

Department of Internal Medicine and Comprehensive Cancer Center, Cancer and Geriatrics Center, the Department of Obstetrics and Gynecology, Department of Biostatistics, School of Public Health, and Biostatistics Core, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan mwicha{at}umich.edu

Objectives: To determine whether a Bcl-xS adenoviral vector has therapeutic potential in an ascites model of human breast cancerin nude mice.

Methods: Advanced ascites were developed by injecting mice intraperitoneally (IP) with MDA-MB-231 human breast carcinoma cells. Mice received sequential IP injections of the Bcl-xS virus or a control lac-Z adenovirus. A third group of mice received no virus. Tumor burden and survival were monitored. Histopathology and necropsies were performed on mice.

Results: A single injection of the Bcl-xS adenovirus produced no systemic or local toxicity and no abnormal histopathology in normal mice. However, abdominal organs within these mice were transduced with the Bcl-xS vector. Adenoviral gene transduction efficiency in MDA-MB-231 ascites was 36 ± 6.40% (n = 3). Percent weight change differences revealed that ascites bearing mice injected three times with the Bcl-xS vector. Adenoviral gene transduction efficiency in MDA-MB-231 ascites was 36 ± 6.40% (n = 3). Percent weight change differences revealed that ascites bearing mice injected three times with Bcl-xS vector showed a statistically significant decrease in tumor burden compared with lac-Z-injected mice (n = 7; P = .012 on days 10-15 after the virst injection). Mice injected with the Bcl-xS vector had significantly greater survival relative to lac-Z-injected mice (n = 7; P = .0004). Bcl-xS protein expression was detected in aspirates of mice injected with the Bcl-xS vector but not the lac-Z vector. Necropsies revealed that ascites bearing mice injected with Bcl-xS vector lacked carcinoma in the peritoneal cavity compared with control mice.

Conclusion: The Bcl-xS adenovirus can reduce tumor burden and increase survival in an ascites model of advanced stage breast cancer.

Key Words: Ascites • Bcl-xS adenovirus • nude mice

Journal of the Society for Gynecologic Investigation, Vol. 7, No. 3, 184-189 (2000)
DOI: 10.1177/107155760000700308
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