A bcl-x(S) adenovirus demonstrates therapeutic efficacy in an ascites model of human breast cancer.
OBJECTIVE
To determine whether a Bcl-x(S) adenoviral vector has therapeutic potential in an ascites model of human breast cancer in 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-x(S) 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-x(S) 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-x(S) 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-x(S) 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 first injection). Mice injected with the Bcl-x(S) vector had significantly greater survival relative to lac-Z-injected mice (n = 7; P = .0004). Bcl-x(S) protein expression was detected in aspirates of mice injected with the Bcl-x(S) vector but not the lac-Z vector. Necropsies revealed that ascites bearing mice injected with Bcl-x(S) vector lacked carcinoma in the peritoneal cavity compared with control mice.


CONCLUSIONS
The Bcl-x(S) adenovirus can reduce tumor burden and increase survival in an ascites model of advanced stage breast cancer.
Sumantran
V N
VN
Department of Internal Medicine and Comprehensive Cancer Center, Cancer and Geriatrics Center, University of Michigan, Ann Arbor, Michigan, USA.
Lee
D S
DS
Baker
V V
VV
Murray
S
S
Strawderman
M
M
Wicha
M S
MS
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis; D001201:Ascites / Q000628:therapy*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010537:Peritoneum / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein