Abstract: LV Ting*, TU Qing-feng, WANG Xiu-li, WANG Hong-wei. *Department of Dermatology, Huadong Hospital, Fudan University, Shanghai 200040, China Corresponding author: WANG Hong-wei, Email: hongweiwang2005@aliyun.com 【Abstract】 Objective To investigate the protective effect of butyl flufenamate ointment against ultraviolet （UV）-induced skin damage, skin aging, and cutaneous squamous cell carcinoma （CSCC） in SKH-1 hairless mice. Methods A total of 128 mice were randomly and equally divided into four groups: UV group receiving UV irradiation only, butyl flufenamate ointment group and matrix cream group receiving UV irradiation after 30-minute pretreatment with topical butyl flufenamate ointment and matrix cream respectively, and blank control group receiving neither pretreatment nor irradiation. In the sunburn experiment （n = 24）, mice were exposed to single session of UV irradiation （1.5 minimal erythema doses （MEDs））, and 24 hours later, erythema and swelling response was observed, and skin tissue was obtained from the irradiated area on the back of mice followed by the determination of COX-2 expression using the streptavidin biotin peroxidase complex （SABC） method. To establish a photoaging （n = 24） and CSCC （n = 80） model, mice were exposed to four sessions of UV irradiation every week for 12 and 28 successive weeks respectively, with the irradiation dose starting at 0.9 MED and increasing gradually. After 12-week irradiation, skin tissue was resected from the back of photoaged mice and subjected to Masson staining for the evaluation of collagen changes as well as immunohistochemical analysis for the quantification of Bax, Bcl-2 and Caspase 3 expression. The initiation and progression of CSCC were observed in mice on a once-a-week basis from 12 to 28 weeks. SPSS 21.0 software was used for statistical analysis. One way analysis of variance was carried out for multiple-group comparisons of numerical data, Ridit analysis for the comparison of immunohistochemical staining intensity. Kaplan-Meier method and log-rank test were utilized for the comparison of tumor-free survival time. Results Both the degree of erythema and swelling response and expression level of COX-2 were significantly lower in the butyl flufenamate ointment group than in the other two UV-irradiated groups （all P < 0.05）. After 12-week irradiation, the butyl flufenamate ointment group showed milder degree of skin aging, together with higher density of collagen in dermis, weaker expression of Bcl-2 but stronger expression of Bax and Caspase 3, by comparison with the other two UV-irradiated groups （all P < 0.05 ）. During the 28 weeks of irradiation, the median tumor-free survival time was statistically longer in the butyl flufenamate ointment group than in the matrix cream group and UV group（（25.0 ± 0.4） months vs. （24.0 ± 0.3） months and （23.0 ± 0.4） months, P < 0.05 and 0.01 respectively）. Conclusion Butyl flufenamate ointment has a certain photoprotective effect. 【Key words】 Butyl flufenamate ointment; Ultraviolet rays; Light; Sunburn; Mice