Abstract | PURPOSE: EXPERIMENTAL DESIGN: Using Lentiviral vectors carrying the HGF transgene, we transduced SK-OV-3 and NIH:OVCAR-3 ovarian carcinoma cell lines to obtain stable autocrine and paracrine HGF receptor activation. In vitro, we assayed growth, motility, invasiveness, and the response to CDDP and paclitaxel of the HGF-secreting bulk unselected cell populations. In vivo, we tested the cytotoxic effects of the drugs versus s.c. tumors formed by the wild-type and HGF-secreting cells in immunocompromised mice. Tumor-bearing mice were treated with CDDP (i.p.) and paclitaxel (i.v.), combined in different schedules and doses. RESULTS: In vitro, HGF-secreting cells did not show altered proliferation rates and survival but were strongly sensitized to the death triggered by CDDP and paclitaxel, alone or in combination. In vivo, we found a therapeutic window in which autocrine/paracrine HGF made tumors sensitive to low doses of the drugs, which were ineffective on their own. CONCLUSIONS: These data provide the proof-of-concept that in vivo gene therapy with HGF might be competent in sensitizing ovarian cancer cells to conventional chemotherapy.
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Authors | Chiara Bardella, Daniela Dettori, Martina Olivero, Nadia Coltella, Massimiliano Mazzone, Maria Flavia Di Renzo |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 13
Issue 7
Pg. 2191-8
(Apr 01 2007)
ISSN: 1078-0432 [Print] United States |
PMID | 17404103
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hepatocyte Growth Factor
- Paclitaxel
- Cisplatin
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Topics |
- Animals
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Apoptosis
- Blotting, Western
- Cell Line, Tumor
- Cisplatin
(therapeutic use)
- Drug Resistance, Neoplasm
(drug effects)
- Female
- Flow Cytometry
- Genetic Therapy
(methods)
- Genetic Vectors
- Hepatocyte Growth Factor
(genetics, metabolism)
- Humans
- In Vitro Techniques
- Lentivirus
(genetics)
- Mice
- Ovarian Neoplasms
(drug therapy, metabolism)
- Paclitaxel
(therapeutic use)
- Reverse Transcriptase Polymerase Chain Reaction
- Transgenes
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