评价HSV-tk/GCV腺病毒候选载体疫苗诱导BALB/c小鼠自噬抑制骨髓瘤肿瘤生长的作用

Shima Poorghobadi, K. Baesi, S. M. Sadat, A. Abdoli, S. Irani
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摘要

引言:本研究的目的是评估含有HSV-TK基因的腺病毒载体候选疫苗在动物模型中对肿瘤减少和自噬机制的影响。方法:用骨髓瘤SP2/0细胞系建立小鼠骨髓瘤模型。形成了阴性对照组、阳性对照组和靶向BALB/c小鼠三组。然后每72小时向靶小鼠注射三次高滴度(108)的Ad HSV-tk/GCV疫苗候选物,并将二甲双胍连续12天注射到对照组中。每三天测量一次所研究的所有15只小鼠的肿瘤大小,最后,在最后一剂疫苗接种三天后,取出肿瘤进行蛋白质印迹和LC3B表达。结果:肿瘤大小检查显示,与阴性对照组相比,注射疫苗和自噬诱导药物可缩小肿瘤大小。Western印迹表明,靶组和阳性对照组的LC3B表达显著高于阴性对照组。(平均差异-0.4921;P值<0.05;q:7.911)。结论:在所研究的动物模型中,Ad HSV-tk/GCV候选疫苗能够诱导自噬并减少肿瘤细胞的生长,这是由于腺病毒诱导免疫系统反应的能力、腺病毒的抗骨髓瘤性和HSV-tk自杀基因的功能。将自杀基因导入腺病毒载体制备病毒疫苗,研究了该疫苗对肿瘤细胞生长和自噬细胞死亡的影响。
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Evaluation of the Effect of HSV-tk/GCV Adenoviral Vector Vaccine Candidate in Inhibiting the Growth of Myeloma Tumors by Inducing Autophagy in BALB/c Mice
Introduction: The aim of this study was to evaluate the effects of an adenoviral vector vaccine candidate containing HSV-TK gene on tumor reduction and autophagy mechanism in animal model. Methods: Myeloma tumor was created in mouse models using myeloma SP2/0 cell line. Three groups of negative control, positive control and target group of BALB/c mice were formed. Candidates for the Ad-HSV-tk /GCV vaccine at high titer (10 8 ) were then injected three times every 72 hours at target mice and metformin was injected into the control group for 12 consecutive days. Tumor size was measured in all 15 mice studied every three days, and finally, three days after the last dose of the vaccine, the tumors were removed for Western blotting and LC3B expression. Results: Examination of tumor size showed that injection of the vaccine and autophagy-inducing drug reduced tumor size compared to the negative control group. Western blotting indicated that LC3B expression was significantly higher in the target and positive control groups than in the negative control group. (Mean Diff: -0.4921; P value < 0.05; q: 7.911). Conclusion: The results suggest that Ad-HSV-tk/GCV vaccine candidate was able to induce autophagy and reduce the growth of tumor cells in the animal model studied due to the ability of adenovirus to induce the immune system response, the anti-myeloma nature of adenovirus and the function of HSV-tk suicide gene. suicide gene in adenovirus vector to make a viral vaccine, we investigated the effect of this vaccine on tumor cell growth and autophagic cell death.
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