肺癌细胞株A549光动力学实验结果的定量分析

Quantitative analysis of photodynamic therapy on lung cancer cell line A549

背景:目前光动力学癌症治疗的基础与临床研究均依赖于经验或定性模型,并缺乏准确有效的光学方法以监测及提高疗效。目的:定量分析光动力数学模型在细胞试验中的应用结果,探讨光动力学疗法治疗计划系统的可能性。方法:将人肺腺癌细胞株A549,3W/633nm半导体二极管激光器,血卟啉衍生物光敏剂Photosan3,采用底部澄清黑色96孔板进行常规细胞培养,严格避光状态下进行光敏剂处理及激光照射,设定标准曲线及对照组,计算不同光功率处理后的细胞残存率;数学模型基于时间域速率方程组方法建立。结果与结论:光敏剂浓度为12g/L、采用20,30,40,50mW4个光照功率、0～20J/cm211个光照能量,组合而成4条细胞残存率曲线,显示激光功率相同情况下,随光照能量增加,细胞残存率下降,且相同能量下,激光功率越高,细胞残存率越高;通过数学模型模拟计算,设定入射光子量ρ为8.0×105,光敏剂初始浓度[S0]i为4.0×1010,初始单态氧浓度[O3]i为5.9×1017,在此参数设定下,模拟的曲线与实际测得曲线最为相近,显示随着入射激光子量增加,细胞残存率逐渐增加,在相同入射光子量之下,细胞残存率随能量增加而下降的趋势。实验结果首次清楚地表明了定量描述光动力学疗法细胞模型的可行性,证实了光动力治疗数学模型与细胞试验的吻合性,表明此模型可以较准确反映细胞试验的结果。

BACKGROUND：Currently,all the basic and clinical researches of photodynamic therapy （PDT） for cancer are based on experience and qualitative models,which lacked of optical methods to monitor the effectiveness.OBJECTIVE：To quantitative analyze the results of PDT quantitative mathematic models in cell test,and to explore the possibility of PDT in the treatment of cancer.METHODS：Human lung cancer cell line A549,a 3W/633 nm semiconductor diode laser and hematoporphyrin derivative Photosan3 were selected.Cells were cultured in clear bottom black 96-hole plate and kept in dark strictly before the different power light treatments.Standard curves and the control groups were set in each plate.The survival ratio of the cell was calculated based on the absorbance and the mathematic models.RESULTS AND CONCLUSION：The four survival curves was made by the power at 20,30,40,and 50 mW,and the eleven illumination energies from 0 to 20 J/cm2,with the photosensitizer concentration was 12 g/L.The survival ratio of the cell decreased as the energies increased when the laser power was the same,and the higher the laser power the more surviving the cells when the energy at the same level.The calculated results showed that,if the incident photon ρ was 8.0×105,the initial concentration of photosensitizeron [S0] was 4.0×1010,and the initial concentration of singlet oxygenthe [O3] was 5.9×1017,the simulative curve was closed to practical curves,illustrating that the cell survival rate was gradually increased with incident photon increasing;under the same incident photon,the cell survival rate was decreased with energy increasing.This is the first study described the feasibility of PDT quantitative mathematic model and proved the coincidence between the calculated value by mathematic model and the experimental results.The simulation results demonstrate the effectiveness of the presented method.