Park Hyunju, Ko Si Hwan, Lee Jae Myun, Park Jeon Han, Choi Youn Hee
Department of Physiology, Tissue Injury Defense Research Center, Ewha Womans University School of Medicine, Seoul, Korea.
Department of Microbiology, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea.
Yonsei Med J. 2016 Nov;57(6):1494-9. doi: 10.3349/ymj.2016.57.6.1494.
The aim of this study was to investigate whether the peroxisomal proliferator-activated receptor gamma (PPARγ) ligand troglitazone in combination with photodynamic therapy (PDT) enhances the apoptotic response of DLD-1 colon cancer cells.
The effects of troglitazone, PDT, and troglitazone in combination with PDT on cell viability and apoptosis were assessed in DLD-1 cells. Cell viability and proliferation were evaluated using the tetrazolium-based MTT assay, and apoptosis was evaluated via cell staining with propidium iodide (PI) and annexin V-FITC. The levels of pro-caspase-3 were measured via Western blot analyses.
Treatment of troglitazone and PDT induced the growth retardation and cell death of DLD-1 cells in a dose-dependent manner, respectively. The combination treatment significantly suppressed cell growth and increased the apoptotic response of DLD-1 and resulted in apoptosis rather than necrosis, as shown by PI/annexin V staining and degradation of procaspase-3.
These results document the anti-proliferative and apoptotic activities of PDT in combination with the PPARγ ligand troglitazone and provide a strong rationale for testing the therapeutic potential of combination treatment in colon cancer.
本研究旨在探究过氧化物酶体增殖物激活受体γ(PPARγ)配体曲格列酮联合光动力疗法(PDT)是否能增强DLD-1结肠癌细胞的凋亡反应。
评估曲格列酮、PDT以及曲格列酮联合PDT对DLD-1细胞活力和凋亡的影响。使用基于四氮唑的MTT法评估细胞活力和增殖情况,通过碘化丙啶(PI)和膜联蛋白V-异硫氰酸荧光素(annexin V-FITC)细胞染色评估凋亡情况。通过蛋白质免疫印迹分析测定前半胱天冬酶-3的水平。
曲格列酮和PDT处理分别以剂量依赖的方式诱导DLD-1细胞生长迟缓及细胞死亡。联合处理显著抑制细胞生长,增强DLD-1细胞的凋亡反应,并导致细胞凋亡而非坏死,PI/膜联蛋白V染色及前半胱天冬酶-3降解结果表明了这一点。
这些结果证明了PDT联合PPARγ配体曲格列酮具有抗增殖和凋亡活性,并为测试联合治疗在结肠癌中的治疗潜力提供了有力依据。