文章摘要
G31P对人肝癌细胞增殖 黏附及侵袭作用的影响
Study on inhibitory effects of G31P on proliferation adhesion and metastasis of human hepatocellular carcinoma cells
投稿时间：2021-03-06  
DOI：10.3969/j.issn.1000-0399.2021.12.003
中文关键词: 肝细胞癌  CXCR1  CXCR2  CXCL8  G31P阻断剂
英文关键词: Hepatocellular carcinoma  CXCR1  CXCR2  CXCL8  G31Pblocker
基金项目:安徽医科大学校科研基金（项目编号：2017xkj054），安徽医科大学校科研基金（项目编号：2019xkj159）
作者单位E-mail
李璐 230000 合肥 安徽医科大学第四附属医院检验科  
陈静静 230000 合肥 安徽医科大学第四附属医院检验科 807233037@qq.com 
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中文摘要:
      目的 探讨原发性肝细胞癌中CXCR1、CXCR2和CXCL8的表达及CXCR1/2受体阻断剂G31P对Hep-G2细胞体外增殖、黏附和侵袭作用的影响。方法 选取2018年12月至2020年12月在安徽医科大学第四附属医院普通外科和肿瘤科接受部分肝切除手术的50例肝癌患者，用免疫组织化学方法，检测癌组织和癌旁组织中CXCR1、CXCR2、CXCL8的表达水平，分析比较CXCR1、CXCR2及CXCL8在肝癌不同临床病理特征中的表达情况。采用Spearman相关分析CXCR1、CXCR2及CXCL8表达与pAKT、pERK、CyclinD1、Bcl-2、VEGF、MMP-9表达量之间的相关性；分别用0、10、50 ng/mL的G31P处理肝癌细胞Hep-G2，每个浓度5个孔，用CCK-8法、ECM实验以及Transwell小室侵袭实验，观察其对Hep-G2增殖、黏附以及侵袭能力的影响。结果 肿瘤组织中CXCR1、CXCR2和CXCL8的阳性率高于相应正常癌旁组织，差异有统计学意义（P < 0.05）；且不同肝癌TNM分期的患者，CXCR1、CXCR2及CXCL8表达差异有统计学意义（P<0.05）；相关分析显示CXCR1与pAKT、pERK、CyclinD1、Bcl-2、MMP-9的表达呈正相关（r=5.824、6.752、6.445、10.503、11.480，P均<0.05），CXCR2与pAKT、pERK、CyclinD1、Bcl-2、MMP-9的表达呈正相关（r=5.219、8.140、5.992、8.672、11.757，P均<0.05），CXCL8与pAKT、pERK、CyclinD1、Bcl-2、MMP-9的表达正相关（r=7.219、6.349、7.018、8.000、8.671，P均<0.05），CXCR1，CXCR2与CXCL8与VEGF的表达无相关性（r=0.095、0.157、0.104，P均>0.05）。体外实验结果显示，与0 ng/mL组相比，50 ng/mL G31P作用24小时后肝癌细胞Hep-G2数量减少（P <0.05）；与0 ng/mL G31P组相比，10 ng/mL G31P组和50 ng/mL G31P组细胞黏附率降低（P<0.05）；与0 ng/mL G31P组以及10 ng/mL G31P组相比，50 ng/mL G31P组穿膜细胞数减少（P<0.05），差异均有统计学意义。结论 原发性肝癌中CXCR1/2和CXCL8的表达明显增加，体外实验表明CXCR1/2受体阻断剂G31P可以明显抑制Hep-G2的增殖、黏附以及侵袭。
英文摘要:
      Objective To investigate the role of CXCR1/2-CXCL8 signal transduction pathway in the development of hepatocellular carcinoma and the inhibitory effects of G31P on the proliferation, migration, invasion and matastasis of HCC.Methods A total of 50 primary hepatocellular carcinoma tissue samples and their adjacent normal tissue samples were retrieved, and we detected CXCR1/2 expression by IHC and discussed its correlation with clinicopathological factors. The inhibitory effects of 0,10,50 ng/mL G31P on the proliferation, adhesion and matastasis of hepatocellular carcinoma cell line Hep-G2 were detected, andthe underlying mechanismwasanalyzed using ECM matrix assay, cell counting kit-8(CCK-8), and Transwell assay.Results Immunohistochemistry demonstrated that the protein levels of CXCR1, CXCR2 and CXCL8 also obviously increased in liver biopsy of HCC(P<0.05). The staining intensity of CXCR1, CXCR2 and CXCL8 in tumor tissues was higher than intheir adjacent normal tissues.In addition, the protein levels of CXCR1,CXCR2 and CXCL8 were significantly associated with TNM staging. The results of spearman correlation analysis showed that the expression of CXCR1/2-CXCL8 was related to the expression of phosphorylation (pAKT, pERK), growth and apoptosis (CyclinD1, Bcl-2), invasion and metastasis (MMP-9) indicators.Compared with 0 ng/mL group, the number of cells treated with 50 ng/mL G31P for 24 hours significantly decreased (P<0.05). Compared with 0 ng/mL G31P group, the cell adhesion rate of 10 ng/mL G31P group and 50 ng/mL G31P group was significantly lower (P<0.05). Compared with 0 ng/mL G31P group and 10 ng/mL G31P group, the number of perforating cells in 50 ng/mL G31P group significantly decreased (P<0.05). Conclusion CXCR1/2-CXCL8 signal transduction pathway plays an important role in the development of HCC.G31P inhibits the proliferation,adhesion and metastasis of Hep-G2 cells in vitro.
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