MDA-7/IL-24 suppresses human ovarian carcinoma growth in vitro and in vivo.
BACKGROUND
Previous studies showed that the human melanoma differentiation-associated gene-7 (mda-7), also known as interleukin-24 (IL-24), has potent antitumor activity against human and murine cancer cells. However, the majority of these studies were limited to in vitro testing. In the present study, we investigated the antitumor activity of mda-7/IL-24 against human ovarian cancer cells both in vitro and in vivo.


RESULTS
In vitro, treatment of ovarian cancer cells with an adenoviral vector carrying the mda-7 gene (Ad-mda7) resulted in inhibition of cell proliferation and induction of cell cycle arrest, leading to apoptosis. We did not observe inhibitory activity in Ad-mda7-treated normal cells. In vivo, treatment of subcutaneous tumor xenografts with Ad-mda7 resulted in significant tumor growth inhibition when compared with that in control groups (p < 0.001). Molecular analysis of ovarian tumor tissue lysates treated with Ad-mda7 showed that MDA-7 protein expression was associated with activation of the caspase cascade.


CONCLUSIONS
Our results show that treatment of ovarian cancer cells with mda-7/IL-24 results in growth suppression both in vitro and in vivo.
Gopalan
Began
B
Department of Thoracic and Cardiovascular Surgery, Unit 445, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. bgopalan@mdanderson.org
Shanker
Manish
M
Chada
Sunil
S
Ramesh
Rajagopal
R
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D015415:Biomarkers; D020169:Caspases; D007378:Interleukins; D000099180:Interleukin-24