Despite aggressive treatment with radiation and
combination chemotherapy following
tumor resection, the 5-year survival rate for patients with
head and neck cancer is at best only 50%. In this study, we examined the therapeutic potential of localized release of
diclofenac from electrospun nanofibers generated from
poly(D,L-lactide-co-glycolide)
polymer.
Diclofenac was chosen since
anti-inflammatory agents that inhibit
cyclooxygenase have shown great potential in their ability to directly inhibit
tumor growth as well as suppress
inflammation-mediated
tumor growth. A mouse resection model of oral
carcinoma was developed by establishing
tumor growth in the oral cavity by ultrasound-guided injection of 1 million SCC-9 cells in the floor of the mouth. Following resection, mice were allocated into four groups with the following treatment: 1) no treatment, 2) implanted scaffolds without
diclofenac, 3) implanted scaffolds loaded with
diclofenac, and 4)
diclofenac given orally. Small animal ultrasound and magnetic resonance imaging were utilized for longitudinal determination of
tumor recurrence. At the end of 7 weeks following
tumor resection, 33% of mice with
diclofenac-loaded scaffolds had a recurrent
tumor, in comparison to 90%-100% of the mice in the other three groups. At this time point, mice with
diclofenac-releasing scaffolds showed 89% survival rate, while the other groups showed survival rates of 10%-25%. Immunohistochemical staining of recurrent
tumors revealed a near 10-fold decrease in the proliferation marker Ki-67 in the
tumors derived from mice with
diclofenac-releasing scaffolds. In summary, the local application of
diclofenac in an orthotopic mouse
tumor resection model of
oral cancer reduced
tumor recurrence with significant improvement in survival over
a 7-week study period following
tumor resection. Local drug release of
anti-inflammatory agents should be investigated as a therapeutic option in the prevention of
tumor recurrence in oral
squamous carcinoma.