多替泊芬-光动力疗法肿瘤抑制效应的实验研究

Inhibition Effects of Photodynamic Therapy with Deuteporfin on Tumor Proliferation both in Vitro and in Vivo

目的观察多替泊芬-光动力疗法(photodynamic therapy,PDT)对肿瘤生长的抑制作用。方法 (1)体外杀伤效应实验,肿瘤细胞加药后孵育3h,采用波长627.8nm、功率密度20mW/cm2的激光照射300s,应用磺酰罗丹明B蛋白染色法(sulforhodamine B,SRB)检测多替泊芬对人口腔鳞癌细胞KB、人结肠腺癌细胞HCT-116、人胃腺癌细胞MKN-45、人宫颈上皮鳞癌细胞HELA、人食管癌细胞Eca-109、人膀胱癌细胞T-24等6株人实体瘤细胞增殖生长的抑制作用。(2)在体抗肿瘤效应实验,荷瘤裸小鼠单次静脉注射多替泊芬后1h,采用波长627.8nm、功率密度120mW/cm2的激光照射肿瘤30min,检测多替泊芬-PDT对裸小鼠人鳞癌KB、人胃腺癌MKN-28、人结肠腺癌HCT-116三种移植肿瘤的生长抑制作用。结果多替泊芬光动力治疗对6株人实体瘤细胞生长抑制的IC50为0.14～0.20μM;加药无激光照射时,对人实体瘤细胞无生长抑制作用。多替泊芬光动力疗法对人鳞癌KB、人胃腺癌MKN-28和人结肠腺癌HCT-116三种裸小鼠移植瘤有明显的生长抑制作用,该作用与药物剂量相关,10mg/kg多替泊芬光动力治疗后第24天上述三种移植瘤的相对肿瘤增值率分别为13.8%、11.7%、14.2%。结论多替泊芬-光动力疗法对本实验的6株人实体瘤细胞、三种实体瘤均有显著生长抑制作用,有较好的临床应用前景。

Objective To investigate the inhibition effects of photodynamic therapy （PDT） with deuteporfin on tumor proliferation. Methods Three hours after incubation with deuteporfin, tumor cells were irradiated with 627.8 nm laser （power density： 20 mW/ cm2） for 300 s. The inhibitory effect of deuteporfin-PDT on the proliferation of KB, HCT-116, MKN45, HELA, Eca-109, and T-24 were measured respectively with Sulforhodamine B （SRB） method. Nude mice with human tumor were given laser irradiation （power density ：120 mW/cm2 , duration：30 minutes） 1 hour after intravenous injection of deuteporfin, and the inhibitory effect of deuteporfin- PDT on tumor proliferation was detected with human tumor nude mice xenografts as models in vivo study. Results The Cytotoxicity ICs0 values of deutepoffin-PDT were between 0. 14 p,M and 0.20 p.M on six human solid tumor cell lines. Without laser irradiation, deuteportin had no inhibitory effect on the proliferation of human solid tumor cell lines. Deuteporfin-PDT had significant inhibitory effect on tumor proliferation of human squamous （KB）, gastroadenocarcinoma （MKN-28）, and colon adenocarci- noma（HCT-116） xenograft models. The inhibitory effect was dosage dependent. The relative tumor proliferation rates of 10 mg/kg deu- teporfin-PDT group were 13.8% , 11.7% and 14. 2% respectively 24 days after the treatment. Conclusions Deuteporfin-PDT has significant proliferation inhibitory effect on solid tumors of different tissue sources.