帕比司他对裸鼠体内人胃肠道间质细胞瘤的治疗作用

Efficacy of Panobinostat To Human Gastrointestinal Stromai Tumors in a Mouse Model

目的：给予移植了人胃肠道间质细胞瘤的裸鼠帕比司他或者联合伊马替尼治疗，评价药物治疗效果。方法：将移植了三种不同KIT外显子突变肿瘤的小鼠随机分为四组，应用帕比司他或者联合伊马替尼对小鼠治疗12天。在确定的时间点取组织病理，对病理标本进行免疫学处理，观察药物对肿瘤细胞的抑制作用。结果：帕比司他对肿瘤细胞产生了明显的抑制作用，联合伊马替尼用药后，肿瘤细胞抑制作用加强，在相同的时间内，用帕比司他单独治疗的小鼠肿瘤减少了62％，而用伊马替尼单独治疗的小鼠肿瘤缩小了25％。这种肿瘤抑制作用在12天后的联合用药组更为明显，肿瘤萎缩了73％。这四组之间的差异就有统计学意义（P〈0．05）。并且减少了细胞的耐药性。结论：帕比司他能够有效地诱导肿瘤细胞的坏死和凋亡，并且在不同程度上抑制肿瘤细胞的增殖。由于帕比司他与伊马替尼联合应用可以克服肿瘤对伊马替尼的耐受作用增强治疗效果，从而为进展期胃肠道间质细胞瘤的治疗提供了一种新的治疗策略。

Objective： Histone deacetylase inhibitors have emerged as potent antieaneer compounds. Using a nude-mouse model under panobinostat / combination panobinostat-imatinib treatment to evaluated the response of gastrointestinal stromal tumors carrying oneogenie KIT（9,11 andl 3） mutations. Methods：We grafted the GIST882 cell line with KIT exon 13 mutation and two biopsies from patients respectively. Our study included 4 groups： A （n= 9）,B （n= 10）,C （n）,and D （n= 8; combination panobinostat--imatinib）. Treatment lasted 12 days. Tumor size was measured and histopathologieal assessment was by H ＆E. Result zIST xenografts responded rapidly to panobinostat. Group D further enhanced the assessed parameters. Conclusion：Our results show exploration of histone deaeetylase inhibitors for the treatment of GISTs.