Sunitinib Improves Some Clinical Aspects and Reverts DMBA-Induced Hyperplasic Lesions in Hamster Buccal Pouch

Abstract

Oral squamous cell carcinoma (OSCC) is a public health problem. The hamster buccal pouch model is ideal for analyzing the development of OSCC. This research analysed the effects of sunitinib (tyrosine kinase inhibitor) in precancerous lesions induced by 7,12-dimethylbenz(a)anthracene (DMBA) in this model. Thirty-four male hamsters, divided into six groups: control-C (n = 7), acetone-A (n = 12), carbamide peroxide-CP (n = 5 ), acetone and CP-A+CP (n = 8), 1% DMBA in acetone and CP-DA+CP (n = 6), and 1% DMBA in acetone and CP and 4-week treatment with sunitinib-DA+CP+S (n = 7). The aspects evaluated were anatomopathological features (peribuccal area, paws, nose, and fur), histological sections of the hamster buccal pouches (qualitatively analyzed), epithelium thickness, and the rete ridge density (estimated). Sunitinib was unable to attenuate the decrease in weight gain induced by DMBA; no increase in volume was detected in the pouch and/or ulceration, observed in 43% of the animals in the DA+CP group. DA+CP groups presented a significant increase in rete ridge density compared to the control groups (P < 0.01) which was reverted by sunitinib in the DA+CP+S group. Sunitinib seems to have important benefits in early stage carcinogenesis and may be useful in chemoprevention.

Figure 1

Weight gain. Weight gained during the experimental period (83 days), expressed in grams, where a = DA+CP ≠ A, b = DA+CP ≠ CP, c = DA+CP ≠ A+CP (P < 0.01), d = DA+CP+S ≠ CP (P < 0.001), and e = DA+CP+S ≠ A+CP (P < 0.01).

Figure 2

Digitized images showing some of the clinical aspects of the animals at the end of the experimental period; note the area of fur loss (star) and fistula (inside the circle) on the animal from the DA+CP group. C: control group, A: acetone group, CP: carbamide peroxide group, A+CP: acetone and carbamide peroxide group, DA+CP: 1% DMBA in acetone and carbamide peroxide group, DA+CP+S: 1% DMBA in acetone and carbamide peroxide, and treatment with sunitinib group.

Figure 3

(a) Epithelial thickness, expressed in µm. (b) rete ridge density, expressed in number of rete ridges/mm, where a is DA+CP ≠ C (P < 0.01), b is DA+CP ≠ A (P < 0.01), c is DA+CP ≠ CP (P < 0.01), d is DA+CP ≠ A+CP (P < 0.001), and e is DA+CP+S ≠ DA+CP (*P < 0.05).

Figure 4

Digitized images of histological sections of the right hamster buccal pouch, stained with hematoxilin and eosin. Note an increased number of rete ridges in the DA+CP group that was reverted by sunitinib in the DA+CP+S group. (a) control group, (b) acetone group in which, acetone was applied 3 times/week, (c) 10% carbamide peroxide which was applied 2 times/week, (d) Acetone + carbamide Peroxide group, (e) DA+CP group, and (f) DA+CP+S group. M: striated muscle, CT: connective tissue, E: epithelium, K: keratin, and arrow: rete ridge.