| Background and Objective:Cutaneous squamous cell carcinoma is the second non-melanoma. It is related to the ultraviolet radiation, virus infection, radiation and exposure to xylene. Health awareness varies greatly from person to person. The disease is more common in the elderly population and low socioeconomic status. It is usually found and treated late. The traditional treatments have high costs and cause high incidence of side effects and financial burden. They could increase psychological distress.As a new treatment tool, PDT was achievement of a good response and got more attention.But the study of photodynamic therapy in cutaneous squamous cell carcinoma mechanism is rare.Studies have showed that abnormal expression of HMGB1 is associated with a variety of clinical tumor disease, and IKKα can result in a related function. The mechanism of HMGB1 and IKKα in photodynamic therapy in cutaneous squamous cell carcinoma and its clinical significance need further research.Comparative experiments were performed to study the effect of photodynamic therapy on the expression of HMGB1 and IKKα in mice of cutaneous squamous cell carcinoma. And then compared with the skin tissue of normal mice. To discuss the mechanistical association between these two important players. And further to explore the value of HMGB1 and IKKα in cutaneous squamous cell carcinoma treatment and prognosis after photodynamic therapy, so as to be used for clinical treatment.Methods:1. To establish a mouse model for cutaneous squamous cell carcinoma induced by 7,12-DMBA/croton oil and NB-UVB. When the diameter of tumor grew to 1-5mm, the total of 20 BALB/c mice which were pathological diagnosis of cutaneous squamous cell carcinoma were randomly divided into four experimental groups. The blank control group were treated with vehicle only. Laser treatment group were treated with the same dose of red light irradiation only. ALA-PDT group were treated with red light irradiation after 20%ALA(wavelength 633 nm,dose 80J/cm2, time 10min),1 times a week, a total of 5 times. ALA group were treated with 20% ALA only. To measure the bidimensional products, tumor volume, tumor number and body weight before treatment every time and 1 week after treatment. When the mice died or the tumor volume reached 500mm3, the reaearch stop. The survival rates of mice in each group were calculated.2. All mice were killed by cervical dislocation at 1 week after the treatment.The tissues of normal mice and skin squamous cell carcinoma micewere cut immediately. Apply RT-PCR and Western blot to detect the changes of HMGB1 and IKKα in cutaneous squamous cell carcinoma and normal skin at the level of gene and protein.3. Apply the statistical software of SPSS19.0 for analysis. All data are presented as mean ± SD(`x ±s). Multiple comparisons were performed with one-way ANOVA, two planned primary comparisons were performed with LSD t. The correlations were performed with spearman rank correlation. Data were analyzed using repeated measurements ANOVA and Dunnett test. A value of P<0.05 was considered to denote statistical significance.Results:1. 1 week after the treatment, ALA-PDT group has showed a marked antitumor effect. The lesions with diameter of 1-3mm and(or) the tumor thickness less than 2mm can be disappeared. The lesions with diameter of 4-5mm and(or) thickness more than 2mm can be partial remised. The number of tumor decreased gradually with the incrase in the number of treatments. The lesions with diameter of more than 5mm had no obvious antitumor effect, tumor volume increased( P<0.05). The lesions of the blank control group and laser treatment group increased and enlarged gradually. Some lesions may coalesce.2. There were 1or 2 mice whose tumor volumes were over 500mm3 in the blank control group,laser treatment group,ALA group except ALA-PDT group. These mice were executed by cervical dislocation. Other mice survived to the end of the experiment. Body weight of mice in each group had no significant difference before and after treatment.3. The expression of HMGB1 m RNA and HMGB1 of lesions in the blank control group, laser treatment group, ALA group and ALA-PDT group were higher than the skin tissue of normal mice,there is significant difference between them(P<0.05).Compared with the blank control group, laser treatment group and ALA group, the expression of HMGB1 m RNA and HMGB1 in ALA-PDT group were higher, there is significant difference between them(P<0.01)4. The expression of IKKα m RNA of the tumor tissue in the blank control group, laser treatment group, ALA group and ALA-PDT group were higher than the skin tissue of normal mice,there is significant difference between them(P<0.05).Compared with the control group, laser treatment group and ALA group, the expression of IKKα m RNA in ALA-PDT group were higher, there is significant difference between them(P<0.01). IKKα was detected in the blank control group, laser treatment group, ALA group and ALA-PDT group except the normal skin tissue. Compared with the blank control group, laser treatment group and ALA group, the expression of IKKα protein in ALAPDT group were higher, there is significant difference between them(P<0.01).5. The expression of IKKα and HMGB1 of the tumor tissue in ALA-PDT group were positively correlated(r=0.948,P<0.05).Conclusion:1. ALA-PDT could effectively remove tumors of 1-3mm in diameter and 2mm in depth, inhibit the growth rate significantly.2. The expression of HMGB1 in squamous cell carcinoma was higher than that of normal skin tissue, IKKα was not expressed in normal skin tissue in mice, but IKKα was high expressed in the lesions of squamous cell carcinoma. HMGB1 and IKKα have a close relationship with the occurrence of the cutaneous squamous cell carcinoma.3. The expression of HMGB1 and IKKα were positively correlation before and after photodynamic therapy. This suggests that the two may have close contact with each other on regulatory photodynamic therapy for the cutaneous squamous cell carcinoma.For further study, we can provide a more practical and effective approach for clinical prevention and treatment of cutaneous squamous cell carcinoma. |
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