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.
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