吉西他滨联合光动力疗法治疗人胰腺癌裸鼠移植瘤的研究

目的 探讨细胞毒药物吉西他滨(gemcitabine)联合光动力疗法(PDT)对人胰腺癌裸鼠移植瘤的疗效.方法 成功造模胰腺癌裸鼠60只,均分为5组:对照组、光敏剂组(光敏素2 mg/kg,腹腔内注射)、化学治疗组(吉西他滨50 mg/kg,腹腔内注射)、光动力组(光敏素2 mg/kg,腹腔内注射+激光照射)和联合治疗组(吉西他滨50 mg/kg+光敏素2 mg/kg+激光照射).光动力组和联合治疗组在光敏素注射48 h后激光照射(630 nm,120 J/cm2),照射时间为20 min;联合治疗组在激光照射前1 h及照射后第3、6、9天腹腔内注射吉西他滨,共4次;化学治疗组吉西他滨剂量、时间与联合治疗组相同.每周2次测虽肿瘤大小,术后21 d处死所有裸鼠,计算瘤体体积,分析各组时一效关系、抑瘤率以及治疗前、后裸鼠体重变化.结果 对照组、光敏剂组和化学治疗组各时段肿瘤体积随时间延长而增长,差异均有统计学意义(P值均＜0.05).光动力组治疗后第6、9、12、15、18和21天肿瘤体积显著小于同时间段的对照组和光敏剂组(P值均＜0.05);联合治疗组第18和21天肿瘤体积明显较光动力组小(P值均＜0.05).联合治疗组和光动力组瘤重分别为(0.29±0.20)g和(0.69±0.23)g,联合治疗组瘤重明显低于光动力组(P＜0.05);以上两组瘤重均比对照组、光敏剂组和化学治疗组低[(1.65±0.21)、(1.62±0.12)和(1.37±0.19)g,P＜0.05].联合治疗组和光动力组抑瘤率分别为82.42%和58.18%,两组比较差异有统计学意义(P＜0.05);且以上两组抑瘤率均高于光敏剂组和化学治疗组(1.80%和17.00%,P＜0.05).结论 PDT能抑制小鼠胰腺癌生长,但维持时间较短;吉西他滨联合PDT能显著抑制小鼠胰腺癌生长,且有协同增效作用.

Study on treatment of transplanted pancreatic cancer by gemcitabine combined with photodynamic therapy

Objective To investigate the effects of gemcitabine,a cytotoxic drug,combined with photodynamic therapy (PDT) in treatment of human pancreatic cancer xenograft in nude mice.Methods The animal model of human pancreatic cancer was developed by suturing small pieces of SW1990 tumors into the dorsum of nude mice.Sixty animal models were randomly divided into five groups with 12 each:control group ( without any treatment ), photosensitizer group ( 2 mg/kg of Photosan, without illumination ),chemotherapy group (receiving 50 mg/kg of gemcitabine i.p. on day 0,3,6 and 9 after transplantation),photodynamic group (2 mg/kg photosan combined with laser irradiation) and combination group (50 mg/kg of gemcitabine and 2 mg/kg of photosan combined with laser irradiation). The tumor sizes were measured twice every week.All mice were sacrificed after 21 days.The tumor volume was calculated,and inhibitory effect and changes before and after treatment were analyzed.Results The tumor was grown bigger in control,photosensitizer and chemotherapy groups (all P value ＜0.05).On day 6,9,12,15,18and 21, the tumor size was significantly smaller in photodynamic group than those in control and photosensitize groups.While the tumor size on day 18 and 21 was smaller in combined group than those in photodynamic group(all P value ＜0.05). The tumor mass was (0.29 ± 0.20) g in combined group,which was lower than that in photodynamic,control,photosensitize and chemotherapy groups[(0.69±0.23) g,(1.65±0.21) g,(1.62±0.12) g,(1.37±0.19) g,respectively,P＜0.05].The inhibitory effect were 82.420%00 and 58.18% in combined group and photodynamic group,respectively(P＜0.05),while there was 1.80% and 17.00% in photosensitize and chemotherapy groups,respectively.Conclusions Photodynamic therapy has significant and short anti-tumor effect,but it can be significantly enhanced by combined with small dose of gemcitabine.