[Inhibiting effects of GW2974 on DMBA-induced hamster buccal pouch carcinogenesis]

To evaluate the inhibiting effects of GW2974, a tyrosine kinase inhibitors, on dimethyl-benzanthracene (DMBA)-induced Syrian golden hamster buccal pouch carcinogenesis.

Ninety hamsters were painted with 0.5% DMBA in the left buccal pouches three times a week for 6 weeks, which were then divided into 3 groups: low-concentration, high-concentration and positive control groups. Positive control group received no further treatment. Ten hamsters served as negative control. The two treated groups were topically painted with GW2974 (4 mmol/L) and GW2974 (8 mmol/L) three times a week, respectively. Tissue samples of the left cheek pouch were obtained at 24 th week. The average number, average volume and burden of tumor, incidence of tumor and the pathological changes of each group were recorded.

After GW2974 (4 mmol/L and 8 mmol/L) was applied topically, tumor incidence decreased from 80.0% (24/30) to 43.3% (13/30, P < 0.01) and 36.7% (11/30, P < 0.01) respectively, the average number of tumors decreased from 1.00 +/- 0.87 to 0.47 +/- 0.82 (P < 0.05) and 0.37 +/- 0.62 (P < 0.05), the average volume and burden of tumors also declined, tumor incidence decreased from 70.0% (21/30) to 40.0% (12/30, P < 0.05) and 33.3% (10/30, P < 0.01), the number of tumors declined from 1.83 +/- 1.91 to 0.67 +/- 0.99 (P < 0.05) and 0.43 +/- 0.68 (P < 0.01).

Topical application of GW2974 could significantly inhibit hamster buccal pouch carcinogenesis, which suggests that GW2974 may have a major impact in chemoprevention and treatment of oral cancer.