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纸质出版日期:2018
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马艳霞, 李黎, 吴勉华, 等. 消癌解毒方对H22荷瘤小鼠移植瘤的抗肿瘤作用机制[J]. 中国实验方剂学杂志, 2018,24(23):140-145.
MA Yan-xia, LI Li, WU Mian-hua, et al. Anti-tumor Mechanism of Xiaoai Jiedu Decoction in Transplanted Tumor of H22 Tumor-bearing Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(23): 140-145.
马艳霞, 李黎, 吴勉华, 等. 消癌解毒方对H22荷瘤小鼠移植瘤的抗肿瘤作用机制[J]. 中国实验方剂学杂志, 2018,24(23):140-145. DOI: 10.13422/j.cnki.syfjx.20182321.
MA Yan-xia, LI Li, WU Mian-hua, et al. Anti-tumor Mechanism of Xiaoai Jiedu Decoction in Transplanted Tumor of H22 Tumor-bearing Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(23): 140-145. DOI: 10.13422/j.cnki.syfjx.20182321.
目的:通过消癌解毒方(XAJD)对H22荷瘤小鼠移植瘤肿瘤组织全基因组芯片的检测以及对相关蛋白的表达影响,探讨其抑制肿瘤的作用机制。方法: ICR小鼠随机分组,接种H22荷瘤小鼠腹水,移植瘤模型成功后,将模型小鼠随机分为空白组,XAJD低、中、高剂量组(10,30,90 g·kg-1·d-1),顺铂组(1 mg·kg-1·d-1)。给药结束,动物处死并取各组动物瘤体组织,无菌生理盐水洗去血渍,称重,计算肿瘤抑制率,取部分新鲜瘤体组织进行全基因组表达谱芯片检测,部分瘤体组织用实时荧光定量PCR(Real-time PCR),蛋白免疫印迹法(Western blot)检测其相关mRNA及蛋白表达。结果:与空白组比较,消癌解毒方低、中、高剂量能够显著降低移植瘤瘤重(P<0.05),消癌解毒方中剂量组与顺铂组效果优于消癌解毒方低、高剂量组(P<0.01),抑瘤率分别达42.8%,58.6%;全基因组芯片检测分析发现,基质金属蛋白酶家族(matrix metalloproteinases,MMPs)和组织金属蛋白酶抑制剂(tissueinhibitor of metalloproteinase,TIMPs)相关蛋白在消癌解毒方不同剂量组中均发生了明显的改变。Real-time PCR,Western blot检测显示,与空白组比较,MMP-9 mRNA及蛋白在消癌解毒方低、中、高剂量组及顺铂组中表达均显著降低(P<0.01),MMP-12 mRNA及蛋白在消癌解毒方中、高剂量组及顺铂组中表达均显著降低(P<0.01),TIMP2 mRNA及蛋白在消癌解毒方中、高剂量组及顺铂组中表达均明显升高(P<0.05)。结论:消癌解毒方能够抑制H22荷瘤小鼠移植瘤生长,可通过抑制MMPs相关蛋白的表达,降低肿瘤的转移和复发可能是其抗癌机制之一。
Objective:To discuss the anti-tumor mechanism of Xiaoai Jiedu decoction(XAJD) through the genome-wide expression profile chip of transplanted tumor in H22 tumor-bearing mice and the expression of related proteins. Method:ICR mice were randomly divided into different groups after inoculating ascites cells from H22 tumor-bearing mice
including blank control group
XAJD low
middle
and high dose groups (10
30
90 g·kg-1) and cisplatin group (1 mg·kg-1). After drug administration
all the animals were killed and transplanted tumor tissues were harvested
washed by sterile saline and weighed to calculate the tumor inhibition rate. Some fresh tumor tissues were used to conduct genome-wide expression profile chip detection and some were used to detect their relevant mRNA expression and protein expression by Real-time polymerase chain reaction (Real-time PCR) and Western blot assay respectively. Result:As compared with blank control group
all of XAJD low
middle and high dose groups could significantly reduce transplanted tumor weight (P<0.05)
and the effect of XAJD middle dose group and cisplatin group were better than those in XAJD low and high dose groups (P<0.01)
reaching an inhibitory rate of 42.8% and 58.6% respectively. The genome-wide expression profile chip analysis showed that matrix metalloproteinases(MMPs) and tissueinhibitor of metalloproteinase(TIMPs) related proteins had obvious changes in different dose groups of XAJD. Real-time PCR and Western blot assay showed that as compared with blank control group
mRNA and protein expression levels of MMP9 were significantly lower in XAJD low
middle
high dose groups and cisplatin group (P<0.01); and the mRNA and protein expression levels of MMP12 were significantly lower in XAJD middle
high dose groups and cisplatin group (P<0.01); while the mRNA and protein expression levels of TIMP2 were significantly higher in XAJD middle
high dose groups and cisplatin group (P<0.05). Conclusion:XAJD can inhibit tumor growth of H22 tumor-bearing mice
and the anti-tumor mechanism might be associated with inhibiting the expression of MMPs related proteins and reducing tumor metastasis and recurrence.
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