甲磺酸伊马替尼增强ALA-PDT对皮肤基底细胞癌细胞杀伤作用研究

Imatinib Mesylate Enhances the Killing Effect of ALA-PDT on Skin Basal Cell Carcinoma Cells

目的:探讨5-氨基酮戊酸(ALA)和/或甲磺酸伊马替尼对HaCaT角质形成细胞、基底细胞癌HSC-2内卟啉含量及ABCG2蛋白表达的影响,为进一步提高PDT的临床疗效提供理论依据。方法:本研究采用表皮HaCaT角质形成细胞、HSC-2基底细胞癌细胞系,在有或无甲磺酸伊马替尼的情况下,用ALA孵育这两种细胞。采用Western-Blotting方法测定ABCG2蛋白含量,ELISA方法检测细胞内卟啉物质的含量,并用共聚焦激光扫描显微镜观察细胞内卟啉物质的定位。结果:研究发现在HaCaT细胞和HSC-2细胞中,与单一ALA与HSC-2细胞作用相比,ALA与甲磺酸伊马替尼联合作用可提高原卟啉物质在HSC-2细胞内的蓄积作用,增强PDT诱导细胞死亡的作用,同时与单一ALA与HSC-2细胞作用相比,ALA与甲磺酸伊马替尼联合作用可显著降低ABCG2蛋白的表达,增强PDT治疗对HSC-2细胞的杀伤作用。结论:本研究揭示了ALA-PDT治疗基底细胞癌敏感性降低的可能原因,为采用ALA-PDT联合甲磺酸伊马替尼进一步提高PDT治疗基底细胞癌的疗效提供理论基础。

Objective:To investigate the effects of 5-aminolevulinic acid(ALA)and/or imatinib mesylate on the content of porphyrin and the expression of ABCG2 protein in HSC-2 of keratinocytes and basal cell carcinoma of HaCaT,and to provide theoretical basis for further improving the clinical efficacy of PDT.Methods:HaCaT keratinocytes and HSC-2 basal cell carcinoma cell lines were cultured with or without imatinib mesylate.The content of ABCG2 protein was determined by Western blotting,the content of porphyrin in cells was detected by ELISA,and the location of porphyrin in cells was observed by confocal laser scanning microscope.Results:In HaCaT cells and HSC-2 cells,the combination of ALA and imatinib mesylate could improve the accumulation of Protoporphyrins in HSC-2 cells,and enhance the cell death induced by PDT.At the same time,compared with the combination of ALA and imatinib mesylate,the combination of ALA and imatinib mesylate could significantly reduce the expression of ABCG2 protein To enhance the killing effect of PDT on HSC-2 cells.Conclusion:This study reveals the possible reasons for the decreased sensitivity of ALA-PDT in the treatment of BCC,and provides a theoretical basis for the further improvement of the efficacy of ALA-PDT combined with imatinib mesylate in the treatment of BCC.