Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality rate.Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer.Hepatocellular carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and recurrence.Nevertheless,the efficacy of FAK phosphorylation inhibitors is currently limited.Thus,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis.This study examined the correlation between FAK expression and the prognosis of HCC.Additionally,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor model.The expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying mechanisms.The results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in vivo.Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited.Consequently,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase

Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains unclear.Therefore,this study aimed to explore the biological function and clinical significance of TROVE2 in hepatocellular carcinoma(HCC).Methods:The expression level of TROVE2 was analyzed in HCC and paired adjacent tissue samples using real-time reverse transcription-quantitative polymerase chain reaction.The impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western blotting.High-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target genes.Back-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC cells.Results:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall survival.Overexpression of TROVE2 facilitated the invasion,metastasis,and epithelial-mesenchymal transition(EMT)process of HCC cells,whereas TROVE2 knockdown restrained migration,invasion,and EMT in these cells.Transcriptome sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of TROVE2.Subsequent back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis effects.Moreover,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3βphosphorylation.Conclusions:TROVE2 facilitated the invasion,migration,and EMT process ofHCC cells through phosphorylation of the HPSE/GSK-3βaxis,indicating its significance as an important protein in tumor progression.

Advances in Research of Post Embolism Syndrome after Transarterial Chemoembolization(TACE)for Hepatocellular Carcinoma

This article reviews the concept and clinical manifestations of post embolism syndrome after transarterial chemoembolization(TACE),and the prevention or timely intervention of post embolism syndrome in advance is expected to reduce its incidence and degree in clinical treatment,and to improve the quality of treatment of Hepatocellular Carcinoma Carcinoma(HCC).

Research Progress of circRNAs during Epithelial- Mesenchymal Transition of Hepatocellular Carcinoma

Hepatocellular carcinoma is prone to invasion and metastasis.It often receives a low diagnosis rate in the early stage but has an extremely high mortality rate.Epithelial-mesenchymal transformation(EMT)is a key factor in promoting tumor cell invasion and metastasis.Circular RNA(circRNA)is involved in regulating EMT in hepatocarcinoma cells through multiple pathways,thereby affecting the occurrence and progression of hepatocellular carcinoma.This article mainly reviews the research progress of circRNA related to EMT core transcription factors,circRNA that promotes EMT in liver cancer,and circRNA that inhibits EMT in liver cancer.

Vascular endothelial growth factor before and after locoregional treatment and its relation to treatment response in hepatocelluar carcinoma patients

Objective:To evaluate vascular endothelial growth factor(VEGF)levels in hepatocellular carcinoma patients before and after transcatheter arterial chemoembolization(TACE)and percutaneous ethanol injection(PEI)and its relation to treatment response.Methods:A total of 40 patients with unrespectable hepatocelluar carcinoma were assessed clinically.Twenty patients were suitable to be treated by TACE,while other 20patients were treated with PEI.Serum VEGF levels were measured before and 1 month after each procedure by ELISA.Response was assessed after 1 month according to Union Internationale Contre le Cancer evaluation criteria based on change in tumor size as measured by ultrasound.Results:There was no significant difference between TACE and PEI groups with regard to age,sex,tumor size,response to local therapy,or VEGF and alpha-fetoprotein before and after therapy.VEGF levels after TACE were significantly higher than before TACE[(298.1±123.6)pg/m L vs.(205.8±307.3)pg/m L;P=0.001].Also,VEGF levels were significantly higher after PEI than before PEI[(333.8±365.6)pg/m L vs.(245.3±301.8)pg/m L;P=0.000].Non-responders of both groups had significantly high VEGF levels than responder's,both before[(985.0±113.2)pg/m L vs.(117.1±75.3)pg/m L;P<0.001]and after therapy[(1 330.6±495.7)pg/m L vs.(171.0±94.7)pg/m L;P=0.000)].Conclusions:Both TACE and PEI were associated with an increase in serum VEGF in hepatocelluar carcinoma patients.Higher levels of VEGF before and after therapy were found in non-responders,suggesting that VEGF is a useful marker in predicting treatment response.

Effects of kanglaite capsules combined with transcatheter arterial chemoembolization （TACE） on patients with mid or late-stage primary hepatocellular carcinoma （HCC）

观察囊与 transcatheter 相结合的 kanglaite (KLT ) 的临床的效果的目的动脉的 chemoembolization (不作声) 在与中间或迟了阶段的主要肝细胞癌(HCC ) 对待病人。65 个盒子随机被划分成 2 个组，的方法在联合组的 32 个病人接受了 KLT 囊 + 的治疗不作声，在控制组的 33 个病人被对待与独自不作声。客观反应率(RR ) ，浆液高山哈 fetoprotein (法新社) ，外部血 T 淋巴细胞亚群(T-LS ) ，生命(QOL ) 的质量，前进(TTP ) 的时间和不利反应在 2 之间被遵守并且比较组。客观反应评估的结果和浆液高山哈 fetoprotein 层次没有在二个组之间的有效差量(P 】 0.05 ) 。联合组是优异的在生命(QOL ) 的质量控制组，前进(TTP ) 的时间，外部血 T 淋巴细胞亚群(CD3+ ， CD4+ ， CD4+&#8726;CD8 比率) 并且肝不利反应，与有效差量(P 【 0.05 ) 。结论 KLT 囊与结合了不作声是到对待的一个有效方法失去了外科的治疗的机会的主要肝细胞癌(HCC ) 病人。

Oncolytic virus-based hepatocellular carcinoma treatment:Current status,intravenous delivery strategies,and emerging combination therapeutic solutions

Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.

Gut Microbiota Modulation:A Viable Strategy to Address Medical Needs in Hepatocellular Carcinoma and Liver Transplantation

Hepatocellular carcinoma(HCC)is the most common malignancy of the liver,posing a significant threat to public health.Although liver transplantation(LT)is an effective treatment for HCC,ischemia–reperfusion(I/R)injury,transplant rejection,and complications after LT can greatly reduce its effectiveness.In recent years,transplant oncology has come into being,a comprehensive discipline formed by the intersection and integration of surgery,oncology,immunology,and other related disciplines.Gut microbiota,an emerging field of research,also plays a crucial role.Through the microbiome–gut–liver axis,the gut microbiota has an impact on the onset and progression of HCC as well as LT.This review summarizes the mechanisms by which the gut microbiota affects HCC and its bidirectional interactions with chronic liver disease that can develop into HCC as well as the diagnostic and prognostic value of the gut microbiota in HCC.In addition,gut microbiota alterations after LT were reviewed,and the relationship between the gut microbiota and liver I/R injury,the efficacy of immunosuppressive drugs used,and complications after LT were discussed.In the era of LT oncology,the role of the gut microbiota in HCC and LT should be emphasized,which can provide new insights into the management of HCC and LT via gut microbiota modulation.

Clinical and Epidemiological Aspects of Hepatocellular Carcinoma at the Internal Medicine Department of Point “G” Teaching Hospital in Mali

Liver cancer is the malignant transformation of liver cells. It develops in 90% of cases of cirrhosis, more rarely on chronic non-cirrhotic liver disease, and exceptionally in a healthy liver. This study aimed to investigate the clinical aspects of Hepatocellular Carcinoma (HCC). It was a retrospective descriptive study covering 10 years, focusing on HCC cases seen in outpatient and inpatient settings at the Internal Medicine Department. We recorded 153 cases out of 7021 patient records, resulting in a hospital frequency of 2.17%. The male-to-female ratio was 3.5. The mean age was 52.37 ± 14.34 years. The most common presenting complaint was pain in 16.3% of cases. A history of jaundice was found in 25.5% of cases. Alcohol consumption was observed in 15.38% of cases. The main physical sign found was hepatomegaly in 76% of cases. HBsAg was positive in 33.3% of cases. Alpha-fetoprotein levels were above 400 IU/ml in 50.81% of cases. Patients classified as CHILD PUGH A represented 39.72% of cases. Abdominal ultrasound revealed portal thrombosis associated with heterogeneous multinodular hepatomegaly in 11% of cases. Cytology confirmed HCC in four out of six patients who underwent the examination. We recorded 63 deaths out of 111 hospitalized patients. Complications included encephalopathy, hematemesis, and ascites in 48 patients. Hepatocellular carcinoma remains a significant public health issue. Its predominance in men and its occurrence in adults with factors such as viral infections and ethylism mean that prevention of this pathology could greatly reduce its incidence.

Treatment of recurrent hepatocellular carcinoma following liver resection,ablation or liver transplantation

Hepatocellular carcinoma(HCC)is the most common primary liver malignancy and causes one third of cancer related deaths world-wide.Approximately one third of patients with HCC are eligible for curative treatments that include hepatic resection,liver transplantation or imaging guided tumor ablation.Recurrence rates after primary therapy depends on tumor biology and pre-treatment tumor burden with early recurrence rates ranging from 30%-80%following surgical resection and ablation.HCC recurs in over ten percent following liver transplantation for HCC.Treatment modalities for tumor recurrence following resection and ablation include repeat liver resection,salvage liver transplantation,locoregional therapies,and systemic chemotherapy/immunotherapy.Locoregional and immune mediated therapies are limited for patients with tumor recurrence following liver transplantation given potential immune related allograft rejection.Given the high HCC recurrence rates after primary tumor treatment,it is imperative for the clinician to review the appropriate treatment strategy for this disease entity.This article will review the current literature regarding HCC recurrence after primary curative therapies and will discuss the relevant future trends in the HCC field.

Xiaoaiping injection affects the invasionand metastasis of hepatocellular carcinomaby controlling AFP expression

Objective Xiaoaiping (XAP) is a traditional Chinese medicine that is a commonly used as an anticancerdrug in clinical practice owing to its high efficiency and low toxicity. Specifically, XAP can effectively inhibitthe growth of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a key HCC diagnostic marker andis closely related to certain malignant cytological behaviors of HCC. However, whether AFP expression andXAP treatment are related to the invasion and metastasis of HCC remains unclear. In the present study, weaimed to evaluate the effects and underlying mechanism of XAP on the invasion and metastasis of HCC..Methods Using a cell scratch assay, Transwell technology, and western blotting we detected the differentinvasion and metastatic abilities of Hep3B cells in XAP treatment and blank control groups. This allowedcomparison of the invasion and metastatic abilities of Hep3B cells with differing levels of AFP expression.AFP mRNA sequencing technology was used to analyze the mechanism of tumor invasion and metastasisassociated with AFP and XAP treatment.Results Cell invasion and metastasis abilities in the XAP group were significantly lower than those in thecontrol group (P < 0.05). Additionally, compared to the control group, the expression of AFP significantlydecreased after XAP treatment (P < 0.05). The ability of Hep3B cells to invade and metastasize waspromoted when AFP expression was up-regulated, whereas it was inhibited when AFP was silenced. XAPinjection and AFP regulate the invasion and metastatic ability of HCC by affecting matrix metalloproteinases(MMPs).Conclusion XAP injection inhibits the invasion and metastatic ability of HCC by influencing the expressionof AFP;additionally, this inhibition of AFP is achieved by affecting MMPs.

JA1体外诱导HCC细胞凋亡的实验研究

采用噻唑蓝(MTT)还原法,测定了梯度浓度的某植物种子粗提物JA1对人肝癌细胞株HCC增殖作用的影响;同时采用流式细胞术、DNA凝胶电泳和透射电子显微镜技术,在体外观察了JA1对HCC细胞凋亡的诱导作用。结果显示,JA1可显著抑制肝癌细胞HCC的增殖,而且这种抑制有浓度依赖性和时间依赖性;流式细胞仪分析表明,经JA1作用后的肝癌细胞HCC检测标本中有明显的DNA低含量颗粒(“亚G1期”峰);凝胶电泳呈现出典型的DNA梯形条带;电镜下出现细胞凋亡典型的形态学改变。

左侧卧位腹腔镜肝右叶部分切除术临床分析

目的探讨左侧卧位腹腔镜肝右叶各肝段部分切除的可行性及疗效。方法回顾性分析右江民族医学院附属医院百东院区2022年5月至2023年4月期间39例行左侧卧位腹腔镜肝右叶部分切除术的病例资料。结果39例中有腹部手术史者13例;肿瘤1个34例,肿瘤2个3例,肿瘤3个2例,肿瘤最大径37.0(24.0,58.0)mm。其中行非解剖性肝切除20例,解剖性肝切除19例;单一肝段切除术28例,两部位肝部分切除术10例,三部位肝部分切除术1例;联合腹腔镜胆囊切除24例;无血流阻断9例,行Pringle法血流阻断30例。平均手术时间(143.5±56.8)min;中位术中出血量100.0(50.0,300.0)mL,4例术中输血(合计29.50 U),无中转开腹。35例放置引流管,引流管留置时间(6.3±3.7)d;术后平均住院时间(10.1±4.0)d,住院总费用(41121.8±18978.3)元。术后23例患者出现少量胸腔积液;1例患者并发急性呼吸窘迫综合征(ARDS)及肝功能不全,经ICU复苏治愈;1例出现少量气胸;无感染、出血、胆漏等并发症发生;无非计划性再次手术发生。所有患者均通过门诊或电话的方式获得随访,所有病例近期无复发。结论左侧卧位行腹腔镜肝右叶部分切除术操作简单,暴露好,手术时间相对较短,出血少。

姜黄素纳米粒(NanoCurc^(TM))联合索拉非尼对肝细胞癌(HCC)的协同抑制作用

目的探讨姜黄素纳米粒(NanoCurcTM,NC)单药或联合索拉非尼对人肝细胞癌(hepatocellular carcinoma,HCC)的作用。方法采用体外细胞增殖检测试剂盒(CCK-8)、体外划痕试验和Transwell侵袭试验法检测NC和/或索拉非尼对肝癌细胞株MHCCLM3增殖、迁移、侵袭能力的影响;应用流式细胞术分析其对细胞凋亡的作用。建立裸鼠MHCCLM3原位移植模型并观察NC和/或索拉非尼对肿瘤大小和肺转移率的影响。应用RTPCR、ELISA、Western blot法检测基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)、细胞外信号调节激酶1/2(ERK1/2)mRNA或相应蛋白表达变化;并测定ERK1/2的磷酸化变化。结果 NC与索拉非尼联合应用可显著抑制HCC体外增殖和侵袭能力(P<0.01),抑制体内肿瘤生长和肺转移(P<0.01)。单独应用NC和索拉非尼时肺转移率分别为50.0%和66.7%,两者联合用药时则显著降低至16.7%。两药联合应用可协同抑制ERK磷酸化,从而下调MMP-9的表达。结论 NC联合索拉非尼可通过协同诱导细胞凋亡、抑制MMP-9的表达而抑制肝癌生长和转移。

HTPAP单体型与基因表达及肝细胞癌(HCC)预后的关系

目的拟通过分析不同HTPAP单体型与基因表达及肝细胞癌(hepatocellular carcinoma,HCC)预后的关系,探讨HTPAP单体型对HCC术后复发及预后的影响。方法随机选取377例HCC样本,提取其中以AGCTAC、GCGGGT、AGCTGC和GCGGAT等4种主要HTPAP单体型组成的HCC RNA。绝对定量PCR检测HTPAP基因表达水平,免疫组化染色、RT-PCR和Western blot检测HTPAP蛋白表达水平,分析单体型与基因表达的关系。随机选取665例HCC样本并提取DNA,焦磷酸测序方法对6个单核苷酸多态性(singlenucleotide polymorphisms,SNPs)进行检测。单体型构建后,分析HTPAP单体型与HCC预后的关系。结果 377例HCC中有327例由上述4种主要单体型构成。基因表达分析提示,HCC中HTPAP在GCGGGT纯合子组和AGCTAC/GCGGGT杂合子组的表达低于AGCTAC/GCGGAT杂合子组、AGCTAC/AGCTGC杂合子组及AGCTAC纯合子组,但差异无统计学意义(P=0.062)。免疫组化染色发现GCGGGT纯/杂合子组HCC较其他单体型HCC的HTPAP表达显著降低(P=0.035)。Kaplan-Meier分析提示,GCGGGT纯/杂合子组HCC较其他单体型HCC术后易复发且预后差(P<0.001)。Cox风险比例模型发现GCGGGT单体型是HCC术后复发及预后差的独立相关因子。结论 HCC的不同HTPAP单体型在mRNA水平的表达差异无统计学意义,但在蛋白水平存在显著差异。GCGGGT单体型可作为HCC术后复发和预后差的预测指标。

肝细胞癌和动脉粥样硬化共表达基因的筛选和验证

目的 通过生物信息学分析鉴定肝细胞癌(Hepatocellular carcinoma, HCC)与动脉粥样硬化(Atherosclerosis, AS)的共表达基因。方法 下载基因表达数据库(Gene expression omnibus, GEO)中肝细胞癌(GSE84402,GSE25097)和动脉粥样硬化(GSE28829,GSE100927)的数据集。使用R软件加权基因共表达网络分析(Weighted gene co-expression networkanalysis, WGCNA)分析GSE84402和GSE28829数据集中共表达基因,Limma鉴定GSE25097和GSE100927数据集中差异表达基因(Differential gene express, DEGs),使用Venny识别WGCNA与差异基因的共表达基因并使用clusterProfiler进行、基因本体(Gene ontology, GO)分析和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析。对WGCNA和差异基因的共表达基因进行qPCR,免疫组织化学技术(Immunohistochemistry, IHC),免疫荧光共定位(Immunofluorescence, IF)等实验验证。结果 WGCNA分析共识别227个共表达基因,差异基因表达分析共识别5个共表达基因,鉴定HIF1A、CASP8、 LEF1、BCAT1、LPL为HCC与AS共表达基因,KEGG分析显示这些基因主要富集在细胞周期和MAPK信号通路,在HCC和AS中qPCR、 IHC、免疫荧光共定位(Immunofluorescence, IF)均显示,共表达基因在病灶组织中的表达均高于对照组织(P<0.05)。结论 HIF1A、CASP8、 LEF1、BCAT1、LPL 5个共表达基因可能是HCC与AS的潜在生物学标志物。同时,MAPK信号通路及细胞周期通路在HCC和AS的发生发展中起到关键作用。

基于整合药理学和转录组学的肝细胞癌和胆管癌共同差异miRNA调控网络构建及相关中药预测分析

目的:利用整合药理学和转录组学方法,构建肝细胞癌与胆管癌共同差异微RNA(miRNA)调控网络,并对关键靶点进行中药预测分析。方法:从GEO数据库获取肝细胞癌、胆管癌芯片数据集,借助在线分析工具GEO_(2)R分析出差异表达miRNA(DEMs)并对其取交集,得到共同DEMs,分别运用FunRich和miRNet软件预测上游转录因子及下游靶基因,并利用DAVID数据库对靶基因进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。借助STRING数据库和Cytoscape 3.9.1软件筛选关键基因(hubGenes)并构建miRNA-hubGenes网络。运用UALCAN、Kaplan Meier-plotter和Coremin Medical数据库对关键基因进行差异表达、总体生存率及相关中药预测分析。结果:肝细胞癌筛选出14个DEMs,胆管癌筛选出104个DEMs, miR-199a-5p为两者共同DEMs,涉及28个上调转录因子,166个下游靶基因;富集分析结果显示,这些靶基因参与肿瘤细胞凋亡、增殖、间质转变和迁移等生物过程,主要通过癌症通路、FoxO信号通路、丝裂原激活的蛋白激酶信号通路以及磷脂酰肌醇3激酶-蛋白激酶B信号通路发挥作用;核心靶点关联中药性味偏微寒,主归肝经,关联最为密切的中药为丹参。结论:miR-199a-5p是肝细胞癌与胆管癌之间重要调控miRNA,丹参干预关键基因出现频次较多,与研究报道基本相符,可为后续肝胆癌机制研究和临床应用提供依据与参考。

m6A去甲基化酶ALKBH5在肝细胞癌发生发展中的功能作用

目的探讨m6A去甲基化酶ALKBH5在肝细胞癌(HCC)发生发展中的功能作用。方法分析公共数据库(TCGA、CPTAC)中ALKBH5在肝癌和癌旁组织中的mRNA和蛋白表达情况。采用qRT-PCR检测ALKBH5在正常肝细胞LO2和肝癌细胞系HepG2、Hep3B和Huh7中的表达;采用siRNA干扰技术和慢病毒技术构建稳定敲减的肝癌细胞株,并检测ALKBH5 mRNA及蛋白质水平的干扰效率;随后通过CCK-8、平板克隆、细胞划痕及Transwell等实验研究ALKBH5对HCC增殖活性及迁移、侵袭能力的影响。结果对TCGA、CPTAC数据库分析显示,相比于癌旁组织,ALKBH5在肝癌组织中的mRNA[(5.78±0.62)vs(5.41±0.25)]和蛋白表达[(0.09±0.35)vs(-0.01±0.16)]水平呈高表达。ALKBH5在正常肝细胞系LO2(1.0±0.1)中的表达显著低于肝癌细胞Hep3B(1430.7±103.9)、Huh7(1515.6±162.4)和HepG2(311.0±29.6)。通过慢病毒法成功构建ALKBH5稳定敲减的Hep3B、Huh7肝癌细胞株。抑制ALKBH5的表达后,Hep3B和Huh7细胞的增殖活性、迁移和侵袭能力均明显减弱(P<0.05)。结论ALKBH5在肝癌细胞中呈高表达,低表达ALKBH5后,对HCC的恶性生物学行为具有抑制作用,但是ALKBH5在HCC中其他的生物学功能及其关联的调控网络仍需进一步探讨。

Caspase12和Caspase3在内质网应激介导的HCC细胞凋亡中的作用

目的探讨Caspase12与Caspase3的表达变化在内质网应激(ERS)介导的肝细胞肝癌(HCC)发生细胞凋亡过程中的作用。方法选取25例临床病理分级为Ⅰ-Ⅱ级(高分化)的HCC组织作为HCCⅠ-Ⅱ级组、25例Ⅲ-Ⅳ级(低分化)HCC组织作为HCCⅢ-Ⅳ级组,分别各取25例癌旁组织作为癌旁对照组;采用原位未端标记法(TUNEL)法检测各组肝组织的细胞凋亡情况,免疫组织化学法、Western Blot检测各组肝组织中Caspase12、Caspase3及GRP78蛋白表达,Real-time PCR检测各组肝组织中Caspase 12、Caspase 3及GRP 78 mRNA表达水平。结果与相应癌旁对照组比较,TUNEL法检测结果表明,HCCⅠ-Ⅱ级、Ⅲ-Ⅳ级组细胞的凋亡数目升高(P<0.05);免疫组织化学法、Western Blot及Real-time PCR检测显示HCCⅠ-Ⅱ级及HCCⅢ-Ⅳ级组中Caspase3与GRP78蛋白及mRNA表达增加(P<0.05);Caspase12蛋白及mRNA表达在各组间比较,差异无统计学意义(P>0.05)。结论ERS参与了HCC发展过程中的细胞凋亡,且是通过介导Caspase12以外的信号通路激活Caspase3执行的细胞凋亡。