联氨基姜黄素诱导DC细胞成熟抑制小鼠皮肤鳞癌进展的机制研究

Study on the mechanism of DC maturation induced by hydrazinocurcumin in inhibiting mouse skin squamous cell carcinoma

目的研究联氨基姜黄素诱导DC细胞成熟抑制小鼠皮肤鳞癌进展的机制。方法梯度浓度(1/5/10/50/100/500μM)的联氨基姜黄素处理SCC细胞系SCL-148 h,MTT检测细胞活性。同时构建自发性SCC小鼠模型,给予药物处理观察肿瘤进展情况,流式检测肿瘤组织树突状成熟状态。Western blot检测联氨基姜黄素处理前后树突状细胞STAT3通路的变化。结果不同浓度的联氨基姜黄素在处理SCC细胞系SCL-1的过程中可能会对细胞的活性产生抑制作用,差异有统计学意义(P<0.05)。半数最大抑制浓度值(IC50)为18.7μM。正常C57BL/6小鼠在为期2周的肠胃给药处理以后,通过与对照组进行比较发现其体重的变化并不显著。自发性SCC小鼠模型在接受联氨基姜黄素处理后,抗肿瘤的效果较为突出,差异有统计学意义(P<0.05)。流式检测SCC小鼠的肿瘤组织,发现联氨基姜黄素处理可促进树突状细胞成熟(CD80/CD86明显上调),差异有统计学意义(P<0.05)。进一步Western blot检测联氨基姜黄素处理前后树突状细胞STAT3通路发现处理组STAT3磷酸化水平显著下调,差异有统计学意义(P<0.05)。结论联氨基姜黄素可在体外杀伤SCC细胞,并在体内促进树突状细胞成熟进而抑制SCC进展,其可能的机制是通过抑制STAT3磷酸化,抑制STAT3通路。

Objective To study the mechanism of DC maturation induced by hydrazinocurcumin in inhibiting mouse skin squamous cell carcinoma.Methods SCC cell line SCL-1 was treated with hydrazinocurcumin at gradient concentration(1/5/10/50/100/500μM)for 48 h,and cell activity was determined by MTT.At the same time,the spontaneous SCC mouse model was constructed,the tumor progression was observed after drug treatment.The dendritic maturation state of tumor tissues was detected by flow.The changes of STAT3 pathway in dendritic cells before and after treatment with hydrazinocurcumin were observed by Western blot.Results Different concentrations of hydrazinocurcumin may inhibit the activity of cells in the treatment of SCC cell line SCL-1,and the difference was significant(P<0.05).The median maximum inhibitory concentration(IC50)was 18.7μM.After normal C57BL/6 mice were given gastrointestinal administration of the drug for two weeks,their weight did not change significantly when compared with the control group.After treatment with hydrazinocurcumin,the antitumor effect of spontaneous mouse model was more prominent,and the difference was significant(P<0.05).Flow cytometry detection of tumor tissues in SCC mice showed that treatment with hydrazinocurcumin could promote dendritic cell maturation(CD80/CD86 was significantly up-regulated),and the difference was statistically significant(P<0.05).Further Western blot analysis of the STAT3 pathway in dendritic cells before and after treatment with hydrazinocurcumin showed that the STAT3 phosphorylation level in the treatment group was significantly down-regulated(P<0.05).Conclusion Hydrazinocurcumin can kill SCC cells in vitro and promote the maturation of dendritic cells in vivo,thus inhibiting the progression of SCC.The possible mechanism is to inhibit the STAT3 pathway by inhibiting the STAT3 phosphorylation.