XIE Bin, XIE Xiong, RAO Bin, et al. Effect of Yiguanjian on JAK1/STAT1 Signaling Pathway and Expression of Downstream Apoptosis Related Proteins in Liver Cancer[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(18): 100-104.
DOI:
XIE Bin, XIE Xiong, RAO Bin, et al. Effect of Yiguanjian on JAK1/STAT1 Signaling Pathway and Expression of Downstream Apoptosis Related Proteins in Liver Cancer[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(18): 100-104. DOI: 10.13422/j.cnki.syfjx.2017180100.
Effect of Yiguanjian on JAK1/STAT1 Signaling Pathway and Expression of Downstream Apoptosis Related Proteins in Liver Cancer
目的:观察一贯煎对肝癌细胞增殖和Janus蛋白酪氨酸激酶/信号转导和转录活化蛋白(JAK1/STAT1)信号通路及其下游凋亡相关蛋白原癌基因(C-myc),B淋巴细胞瘤-2(Bcl-2),p53表达的影响。方法:雄性昆明小鼠50只,随机均分为模型组,环磷酰胺[CTX,50 mg ·kg-1 ·(2 d)-1]组,一贯煎高、中、低剂量(46,23,11.5 g ·kg-1 ·d-1)组。腋下注射H22细胞建立小鼠荷瘤模型,一贯煎高、中、低剂量组造模前两周开始用药,CTX组造模后开始给药,模型组造模后灌胃等体积生理盐水,造模后继续给药2周。处死各组小鼠,取瘤组织称重,免疫组织化学法检测肿瘤组织JAK1,STAT1蛋白磷酸化水平,蛋白电泳法检测C-myc,Bcl-2,p53蛋白的表达。结果:与模型组比较,一贯煎(46,23,11.5 g ·kg-1 ·d-1)及CTX均具有显著的抑瘤作用(P<0.01);一贯煎高、中剂量均可明显降低JAK1蛋白磷酸化水平(P<0.05),明显提高STAT1蛋白磷酸化水平(P<0.05);一贯煎高剂量可明显降低C-myc蛋白表达,并促进p53蛋白表达,一贯煎高、中剂量可明显降低Bcl-2蛋白表达(P<0.05,P<0.01)。结论:一贯煎能抑制肝癌细胞增殖,其机制可能与控JAK1/STAT1磷酸化,促进其下游p53蛋白表达,抑制其下游C-myc,Bcl-2蛋白表达,从而促进肝癌细胞凋亡有关。
Abstract
Objective: To observe the effect of Yiguanjian on growth of liver cancer
Janus protein tyrosine kinase/signal transducers and transcriptional activator proteins (JAK1/STAT1) signaling pathway
as well as the expression of downstream apoptosis related proteins C-myc
B-cell lymphoma-2 (Bcl-2)
and p53.Method: The 50 male KM mice were randomly divided into model group
cyclophosphamide[CTX
50 mg · kg-1 · (2 d)-1] group
and Yiguanjian high
middle
and low dose groups (46
23
11.5 g · kg-1 · d-1). H22 tumor cells were injected under armpit to establish tumor-bearing mice models. Treatment began two weeks before modeling in Yiguanjian high
medium and low dose groups. CTX was administrated after modeling and the mice in model group were administrated with the same volume of normal saline after modeling 2 weeks before and after modeling. The mice in various groups were sacrificed
and their tumor tissues were taken and weighed. Then the JAK1 and STAT1 protein phosphorylation levels were detected by immunohistochemistry and C-myc
Bcl-2 and p53 protein expression levels were detected by protein electrophoresis.Result: As compared with model group
there was a significant inhibition effect on tumors in Yiguanjian high
medium
low dose groups and CTX group (P<0.01); high dose and middle dose Yiguanjian could significantly reduce JAK1 protein phosphorylation level (P<0.05) and significantly increase STAT1 protein phosphorylation level (P<0.05); high dose Yiguanjian could significantly reduce protein expression of C-myc and promote the protein expression of p53 (P<0.05); high and middle dose Yiguanjian could significantly decrease the protein expression of Bcl-2 (P<0.05
P<0.01).Conclusion: Yiguanjian had obvious antitumor effect probably by regulating JAK1/STAT1 phosphorylation