携带颗粒溶素活性肽基因的减毒沙门菌对小鼠黑色素瘤的治疗作用

Curative Effect of Attenuated Salmonella Carrying Active Peptide Gene of Granulysin on Melanoma in Mice

目的观察携带颗粒溶素(Granulysin,GLS)活性肽基因的减毒沙门菌对小鼠黑色素瘤的治疗作用。方法将小鼠黑色素瘤细胞株B16接种C57 BL/6J小鼠,复制小鼠黑色素瘤模型。将pBudCE4.1-S9K重组沙门菌以不同剂量及不同时间接种于小鼠肿瘤内,检测肿瘤体积,确定最佳治疗剂量和起始时间。将模型小鼠随机分为PBS组、减毒沙门菌组、pBudCE4.1重组沙门菌组和pBudCE4.1-S9K重组沙门菌组,分别采用最佳治疗剂量,在最佳治疗起始时间开始治疗,每周1次,共3次。从成瘤开始,每2 d测量肿瘤的最长径(L)和最短径(S),计算肿瘤体积,绘制肿瘤生长曲线,并观察小鼠的荷瘤存活期。结果小鼠黑色素瘤模型复制成功。重组沙门菌的最佳治疗剂量和起始时间分别为107个/ml和第4天。与PBS组、减毒沙门菌组和pBud-CE4.1重组沙门菌组相比,pBudCE4.1-S9K重组沙门菌组能明显抑制模型小鼠肿瘤的生长,使肿瘤体积增长延缓,并明显延长荷瘤小鼠的存活期。结论 pBudCE4.1-S9K重组减毒沙门菌对小鼠黑色素瘤具有一定的治疗作用。

Objective To observe the curative effect of attenuated salmonella carrying active peptide gene of granulysin（GLS） on melanoma in mice.Methods C57 BL / 6J mice were inoculated with murine melanoma cell B16 strain to copy mouse model of melanoma.Recombinant salmonella with plasmid pBudCE4.1-S9K at various dosages were inoculated into the tumors of model mice,and the tumor sizes were measured,based on which the dosage and initial time for treatment were optimized.The model mice were divided into four groups,and treated with PBS,attenuated salmonella,recombinant salmonella with plasmid pBudCE4.1 and recombinant salmonella with plasmid pBudCE4.1-S9K respectively,at optimal dosages and initial times,once a week for 3 times.The tumors were measured for the longest（L） and the shortest（S） diameters every 2 d starting from their formations,based on which the tumor sizes were calculated,and a tumor growth curve was plotted.The survival periods of tumor-bearing mice were observed.Results Mouse model of melanoma was successfully copied.The optimal dosage and initial time of recombinant salmonella for treatment were 107 bacillus / ml and day 4 after inoculation with B16 cells respectively.Recombinant salmonella with plasmid pBudCE4.1-S9K inhibited the tumor growth significantly,decreased the tumor growth rate and increased the survival period of tumor-bearing mice as compared with PBS,attenuated salmonella and recombinant salmonella with plasmid pBudCE4.1.Conclusion Recombinant attenuated salmonella with plasmid pBudCE4.1-S9K showed a certain curative effect on melanoma in mice.