Background: Free flap-mediated gene therapy in the tumor bed following surgical resection is a promising approach in cancer targeted treatment of residual disease. We investigated the selective killing efficacy of a lentivirus-mediated cytosine deaminase-thymidine kinase (CDglyTK) gene in transplanted breast cancer delivered into a free flap by intra-artery perfusion.

Methods: Proliferation, apoptosis, and cell cycle of rat SHZ-88 breast cancer cells transfected with a lentivirus-mediated CD/TK gene were measured following treatment with ganciclovir and 5-flucytosine in vitro. A model of residual disease of breast cancer in a rat superficial inferior epigastric artery (SIEA) flap model was used to study the therapeutic potential of a double suicide CD/TK and prodrug system in vivo.

Results: Killing efficacy of the double suicide CD/TK and prodrug system on SHZ-88 cells was mediated by increased apoptosis and cell cycle arrest at the G1 phase with significant bystander effect. Following recombinant lentivirus transfection of rat SIEA flap by intra-artery perfusion, CD/TK gene expression was limited to the flap, and the volume and weight of transplanted tumors were significantly reduced without observable toxicity.

Conclusions: SIEA flaps transfected with a lentivirus-mediated CDglyTK gene by intra-artery perfusion effectively suppress transplanted breast tumor growth without obvious systemic toxic effects in rats.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744674PMC
http://dx.doi.org/10.1186/s12885-019-6111-5DOI Listing

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