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褪黑素对小鼠皮下移植性胰腺癌的作用

Effect of melatonin on the pancreatic cancer in mice subcutaneous xenograft

摘要目的 探讨褪黑素(MT)对Balb/c裸鼠胰腺癌皮下移植瘤的治疗作用.方法 建立Balb/c小鼠皮下胰腺癌移植瘤模型,分别用生理盐水(对照组)、低剂量MT(10 mg·kg-1·d-1)、高剂量MT(20 mg·kg-1·d-1)、吉西他滨(GEM,50 mg·kg-1·d-1)及GEM+高剂量MT(联合)干预,定期测量肿瘤大小,绘制肿瘤生长曲线,并用MTT法检测小鼠脾脏自然杀伤细胞(NK)活性.结果 对照组移植瘤体积为(1.476±0.075)cm3,低剂量MT组、高剂量MT组、GEM组和联合组的移植瘤体积分别为(0.998±0.112)cm3、(0.756±0.128)cm3、(0.746±0.115)cm3和(0.305±0.111)cm3,较对照组显著缩小(P值均<0.01),并且高剂量MT组移植瘤体积较低剂量MT组小,联合组移植瘤体积最小.对照组NK细胞的杀伤活性为(18.07±1.23)%,低剂量MT组、高剂量MT组和联合组NK细胞的杀伤活性分别为(44.27±3.19)%、(45.16±3.20)%和(30.29±2.91)%,较对照组显著增强(P值均<0.01);GEM组NK细胞的杀伤活性为(14.24±2.70)%,较对照组显著减弱(P<0.05),而联合组NK细胞的杀伤活性显著高于GEM组(P<0.01).结论 MT能增强荷瘤裸鼠的免疫功能,抑制移植性胰腺癌的生长,与吉西他滨联合应用,则肿瘤抑制作用更强.

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abstractsObjective To investigate the therapeutic effects of melatonin (MT) on human pancreatic cancer in Balb/c nude mice subcutaneous xenograft model. Methods Pancreatic cancer model was established high dose MT(20 mg· kg -1 · d-1 ) , gemcitabine( GEM,50 mg· kg -1 · d-1 ) and high dose MT combination with GEM. Tumor size was measured regularly. The tumor growth curve was drawn. The activity of mice spleen natural killer cell was determined by MTT. Results Compared with the controls [ ( 1. 476 ± 0.075) cm3 ], tumor volumes in low dose MT group[ (0.998 ±0.112)cm3], high dose MT group[ (0.756 ±0.128) cm3], GEM group [ (0. 746 ± 0. 115 ) cm3 ], combination group [ (0. 305 ± 0. 111 ) cm3 ] were significantly decreased ( P <0.01), and the tumor size in high dose MT group was smaller than that in low dose MT group, while the tumor size in combination group was the smallest. The activity of mice spleen natural killer cell was ( 18.07 ± 1.23) %in control group, and they were (44.27 ±3.19)% ,(45.16 ±3.20)% and (30.29 ±2.91)% in low dose MT group, high dose MT group, combination group, which were significantly higher than those in the control group;the activity of natural killer cell in GEM group was ( 14.24 ± 2.70) %, which was significantly lower than that in the control group (P <0.05), but the activity of natural killer cell in combination group was significantly higher than that in the GEM group (P < 0.01 ). Conclusions MT could improve the immune function of mice,inhibit the growth of tumor, and MT combination with GEM may have more potent antitumor effect.

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