Clinicopathological features of hepatocellular carcinoma evaluated by vascular endothelial growth factor expression

AIM: To evaluate the significance of the expression of vascular endothelial growth factor (VEGF), its correlation with clinicopathological variables were studied in the tissue of hepatocellular carcinoma (HCC) and surrounding liver. METHODS: In 56 samples (tumor and non-tumor liver tissue) collected from 28 patients, VEGF expression was examined by immunohistochemistry and western blot analysis. RESULTS: The value of VEGF expression by western blotting was correlated with immunohistochemical staining grade. In tumor tissue, the value of VEGF expression correlated with tumor size (P = 0.034), á-fetoprotein (P = 0.036) and protein induced by vitamin K absence-II by simple regression, and histological grade (P = 0.0132) by the unpaired t-test. The level of VEGF expression in non-tumor liver was found to correlate with the value of serum albumin (P = 0.008), cholinesterase (P = 0.012) and prothrombin activity (P = 0.046). The frequency of simple nodular type in gross appearance decreased in cases with high tumor/non-tumor (T/N) ratio (P = 0.022), and the degree of portal vein invasion progressed with an increase in the T/N ratio (P = 0.008). The T/N ratio was significantly higher in early recurrence cases (P = 0.0081). CONCLUSION: This study on the expression of VEGF might be useful to estimate the liver condition and the clinicopathological features of HCC.     

Gross appearance of hepatocellular carcinoma reflects E-cadherin expression and risk of early recurrence after surgical treatment

BACKGROUND AND AIMS: Correlation between the gross classification of hepatocellular carcinoma (HCC) and its vascular invasion or intrahepatic metastasis has been reported previously. Because E-cadherin-mediated epithelial cell-to-cell adhesion is thought to suppress cancer cell invasion, the present study was performed to analyze the correlation between E-cadherin expression and the gross classification of HCC. METHODS: Thirty-six resected solitary HCC <6 cm in diameter were each classified as single nodular type (type 1), single nodular with extranodular growth type (type 2) or contiguous multinodular type (type 3), and the clinicopathological and prognostic differences between type 1 HCC and the other types were analyzed. The expression of E-cadherin in each tumor was examined by immunoblotting and immunohistochemical analysis. RESULTS: Vascular invasion and microscopic intrahepatic metastasis were observed more frequently in types 2 and 3 (61%) than in type 1 (13%) HCC. Immunoblot analysis indicated that the relative level of E-cadherin expression in cancerous tissue was significantly lower in type 2 and 3 (0.75 +/- 0.49) than in type 1 (1.46 +/- 0.79) HCC. Immunohistochemical examination revealed decreased and partially absent E-cadherin expression in the tumorous area of type 2 and 3 HCC. The recurrence-free survival rate was higher for patients with type 1 HCC than for those with the other types. CONCLUSIONS: Types 2 and 3 HCC have marked metastatic and invasive potential and reduced expression of E-cadherin, predicting a high risk of recurrence after surgical treatment.     

Useful detection of CD147 （EMMPRIN） for pathological diagnosis of early hepatocellular carcinoma in needle biopsy samples

AIM To make clear whether CD147 (EMMPRIN)expression in pathological tumor samples with a fineneedle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC).METHODS Twenty-two patients (15 men and 7 women;median age 68 years, range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC.Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition, the degree of staining within tumor tissue was compared according to a number of clinicopathological variables.RESULTS The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues, even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP.CONCLUSION CD147 serves potentially as a pathological target for cancer detection of early HCC.     

c-Met represents a potential therapeutic target for personalized treatment in hepatocellular carcinoma

c-Met, a high-affinity receptor for hepatocyte growth factor (HGF), plays a critical role in cancer growth, invasion, and metastasis. Hepatocellular carcinoma (HCC) patients with an active HGF/c-Met signaling pathway have a significantly worse prognosis. Although targeting the HGF/c-Met pathway has been proposed for the treatment of multiple cancers, the effect of c-Met inhibition in HCC remains unclear. The human HCC cell lines Huh7, Hep3B, MHCC97-L, and MHCC97-H were used in this study to investigate the effect of c-Met inhibition using the small molecule selective c-Met tyrosine kinase inhibitor PHA665752. MHCC97-L and MHCC97-H cells demonstrate a mesenchymal phenotype with decreased expression of E-cadherin and increased expression of c-Met, fibronectin, and Zeb2 compared with Huh7 and Hep3B cells, which have an epithelial phenotype. PHA665752 treatment blocked phosphorylation of c-Met and downstream phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/Erk pathways, inhibited cell proliferation, and induced apoptosis in c-Met-positive MHCC97-L and MHCC97-H cells. In xenograft models, administration of PHA665752 significantly inhibited c-Met-positive MHCC97-L and MHCC97-H tumor growth, and PHA665752-treated tumors demonstrated marked reduction of both c-Met phosphorylation and cell proliferation. c-Met-negative Huh7 and Hep3B cells were not affected by c-Met inhibitor treatment in vitro or in vivo. In addition, c-Met-positive MHCC97-L and MHCC97-H cells demonstrated cancer stem cell-like characteristics, such as resistance to chemotherapy, tumor sphere formation, and increased expression of CD44 and ABCG2, and PHA665752 treatment suppressed tumor sphere formation and inhibited CD44 expression. Conclusion: c-Met represents a potential target of personalized treatment for HCC with an active HGF/c-Met pathway.     

Clinicopathological significance of expression of paxillin, syndecan-1 and EMMPRIN in hepatocellular carcinoma

AIM: To evaluate the relationship of expression of paxillin, syndecan-1 and EMMPRIN proteins with clinicopathological features in hepatocellular carcinoma (HCC). METHODS: Fifty-one patients who underwent HCC resection were recruited in the study. Paxillin, syndecan-1 and EMMPRIN proteins in HCC tissues were detected with immunohistochemical staining. RESULTS: Of 51 cases of HCC, 23 (45%) exhibited paxillin protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 24 (57%) exhibited positive expression. Positive paxillin protein expression was associated with low differentiation (r= 0.406, P= 0.004), with the presence of portal vein thrombosis (r = 0.325, P = 0.021), with extra-hepatic metastasis (r=0.346, P=0.014). Of 51 cases of HCC, 28 (55%) exhibited syndecan-1 protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 23 (55%) exhibited positive expression. Positive snydecan-1 protein expression was associated with well differentiation (r=0.491, P=0.001), with no extra-hepatic metastasis (r=0.346, P=0.014). Of 51 cases of HCC, 28 (55%) exhibited EMMPRIN protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 21 (50%) exhibited positive expression. Expression of EMMPRIN protein was not associated with serum AFP level, HBsAg status, presence of microsatellite nodule, tumor size, presence of cirrhosis and necrosis, differentiation, presence of portal vein thrombosis, extra-hepatic metastasis, disease-free survival and overall survival (P>0.05). Expression of paxillin protein was correlated conversely with the expression of syndecan-1 protein in HCC (r = -0.366, P = 0.010). CONCLUSION: Expression of paxillin and syndecan-1 proteins in HCC may affect its invasive and metastatic ability of the tumor. There may be a converse correlation between the expression of paxillin and syndecan-1 protein in HCC. Expression of EMMPRIN protein may be detected in HCC, but it may play little role in the invasion and metastasis of HCC.     

Glypican-3蛋白在肝细胞癌患者血清和组织中的表达及意义

目的:探讨肝细胞癌(HCC)患者血清和组织中Glypican-3(GPC3)蛋白的表达及临床意义.方法:收集HCC患者27例和肝良性病变患者28例的术前1d空腹血清及组织标本,采用Western blot检测血清中GPC3蛋白,同时采用免疫组织化学SP法检测组织标本中GPC3的表达情况.结果:27例HCC患者HCC组织、癌旁组织和远癌肝组织中GPC3蛋白阳性的表达率分别为81.5%,0%和0%(HC:23.4689,P<0.001),术前血清中GPC3蛋白阳性率分别为55.6%;28例肝良性病变患者组织和血清中阳性率均为0%;GPC3蛋白对HCC诊断的敏感性为55.6%,特异性为100%,误诊率为0%.HCC患者血清中GPC3蛋白表达与其瘤体大小和病理分级之间差异有显著性(P<0.05),而与患者年龄、性别、HBsAg及AFP值之间差异无显著性(P>0.05).结论:GPC3蛋白在HCC患者血清和组织中有较高的表达,对诊断HCC有较高的敏感性和特异性,可作为HCC早期诊断的标志物.     

Gene expression of hepatocyte growth factor and its receptor in HCC and nontumorous liver tissues

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Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis

OBJECTIVE: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that has been implicated in cancer growth, tissue development, and wound repair. Its actions are dependent on activation by HGF activator (HGFA) and its binding to a specific HGF receptor (c-Met). We examined the role of HGF, HGFA, and c-Met in synovial tissues in rheumatoid arthritis (RA) and osteoarthritis (OA), and their localization and mRNA expression. METHODS: Immunohistochemical staining, Western blotting, RT-PCR, and in situ hybridization (ISH) for HGF, HGFA, and c-Met were performed on synovial tissue specimens from 10 patients with RA and 4 with OA, and 2 healthy controls. RESULTS: Immunohistochemical staining revealed that HGFA and c-Met were strongly expressed in fibroblasts, macrophages, endothelial cells, and synovial lining cells. HGF was expressed only faintly in macrophages and fibroblasts, and not at all in the endothelial cells of RA and OA synovial tissue. HGFA was detected near 73 and 34 kDa on Western blot analysis, corresponding to inactive and active HGFA, respectively. RT-PCR showed HGF, HGFA, and c-Met mRNA in RA, OA, and control synovial tissue. ISH and immunohistochemistry revealed mRNA expression for HGF, HGFA, and c-Met in the cell types mentioned above. CONCLUSION: HGFA, HGF, and c-Met mRNA are expressed in synovial tissue in RA and OA, and HGF is activated by HGFA and binds to c-Met on endothelial cells, inducing angiogenesis.     

PTEN和磷酸化Smad2在原发性肝癌中的表达

目的探讨肝癌等组织中10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）和磷酸化Smad2（P-Smad2）表达的意义。方法采用免疫组织化学技术检测肝癌组织、癌旁肝组织和非癌性肝组织中P-Smad2和PTEN的表达。结果31份肝癌组织中PTEN表达以细胞质和细胞膜明显,细胞核基本不表达；25份癌旁及13份非癌性肝组织中则以细胞核和细胞质强表达,细胞膜弱表达。PTEN在肝癌组织的表达率（64．5％）低于癌旁肝组织（96．0％）和非癌性肝组织（100．0％）,表达强度（4．19±3．31）低于癌旁肝组织（7．88±0．93）和非癌性肝组织（7．77±0．93）,差异均有统计学意义（P＜0．05）。不同病理分级的肝癌组织中PTEN的表达率差异无统计学意义（P＞0．05）,≥Ⅱ级的肝癌组织细胞质表达强度（3．07±2．87）低于＜Ⅱ级（5．80±3．12）的肝癌组织（P＜0．05）。癌旁有、无肝内血管癌栓的肝癌组织中,PTEN表达率分别为45．5％和85．7％,表达强度分别为3．00±3．46和6．28±2．37,差异均有统计学意义（P＜0．05）。PTEN在肝细胞的表达定位与病理类型呈负相关（r=0．34,P＜0．01）,与肝内血管癌栓呈负相关（r=-0．43,P＜0．05）。非癌性肝组织、癌旁肝组织和病理分级＜Ⅱ级的肝癌组织中,P-Smad2表达以细胞核和细胞质明显,≥Ⅱ级的肝癌组织中则以细胞核为主。P-Smad2在肝细胞的表达定位与病理类型呈正相关（r=0．22,P＜0．05）,P-Smad2在细胞核的表达强度。肝癌组织与癌旁肝组织的差异无统计学意义,也与肝内血管有无癌栓无关。肝癌组织中PTEN和P-Smad2表达呈负相关（r=-0．73,P＜0．01）。结论PTEN的表达、强度以及和P-Smad2的核、质转位可能与肿瘤的发展和恶化有关,二者可能存在相互作用,共同参与肝癌的发生机制。     

Overexpression of p28／gankyrin in human hepatocellular carcinoma and its clinical significance

AIM：To investigate the expression of p28/gankyringene and its role in the carcinogenetic process of human hepatocellular carcinoma(HCC).METHODS:64specimens of HCC and para-carcinoma tissues,22specimens of non-tumor liver tissues(7normal,15cirrhosis),10 specimens of normal human tissues and 5hepatoma cell lines were studied for the expression of p28/gankyrinby Northern blot.The expressionof p28/gankyrin protein was detected immunohistochemically by using the specific polyclonal antibody.RESULTS:Northern blot analysis indicated that the expression of p28/gankyrinmRNA was intensively distributed in brain and heart,weakly in lung,spleen and muscle,undetectable in digestive system including liver,pancreas,stomach,small and large intestines.p28/gankyrinmRNAwas absent in normal liver,weakly detected in liver cirrhosis and in 18of 64para-carcinoma liver tissues.In contrast,the expression of p28/gankyrinmRNA was intensitely detected in all5hepatoma cell lines tested,markedly increased in 57of 64and moderately increased in 5of64HCCsamples.In comparison with liver cirrhosis and para-carcinoma liver tissues.the average expression of p28/gankyrinmRNAin HCCwas increased3.6-(2.901&#177;0.507vs0.805&#177;0.252,P&lt;0.05)and5.2-fold(2.901&#177;0.507vs0.557&#177;0.203,p&lt;0.01),respectively.In addition,p28/gankyrinmRNA expression level was higher in HCCwith portal vein tumor thrombus and microscopic hepatic vein involvement(P=0.021and P=0.047,respectively).Theoverexpression of p28/gankyrin protein in HCCwas targeted in hepatic tumor cells,not in bile duct cells and other interstitial cells.Plays an important role and contributes to the metastasis potential in the process of carcinogenesis.p28/gankyrinmay become a specific biological tissue marker for the pathological diagnosis of HCC.     

Impairment of the antifibrotic effect of hepatocyte growth factor in lung fibroblasts from African Americans: possible role in systemic sclerosis

OBJECTIVE: To compare the composition of cytokines in African American and Caucasian patients with systemic sclerosis (SSc; scleroderma) and in healthy individuals, particularly the expression and function of hepatocyte growth factor (HGF). METHODS: Bronchoalveolar lavage (BAL) fluid samples were analyzed using cytokine array techniques. HGF in plasma and cell culture medium samples was measured by enzyme-linked immunosorbent assay. Connective tissue growth factor (CTGF), type I collagen expression, and c-Met receptor phosphorylation were studied by immunoblotting. RESULTS: Overall greater expression of cytokines in BAL fluid from African American patients as compared with Caucasian patients was observed. Significant increases in HGF concentrations were detected in BAL fluid, plasma, and fibroblast culture medium from Caucasian SSc patients. In contrast, African American SSc patients did not demonstrate an increase in HGF. Recombinant HGF readily abolished CTGF expression and collagen accumulation in lung fibroblasts isolated from Caucasian SSc patients. Pretreatment of lung fibroblasts with neutralizing anti-c-Met antibody abolished the effects of HGF on CTGF expression and collagen accumulation, suggesting that the antifibrotic activity of HGF is mediated via c-Met receptor tyrosine kinase. Whereas recombinant HGF rapidly induced c-Met receptor phosphorylation in lung fibroblasts from Caucasian patients, c-Met receptor phosphorylation was significantly reduced in lung fibroblasts from African American subjects. Moreover, recombinant HGF failed to prevent CTGF expression and collagen accumulation in lung fibroblasts derived from African American subjects. CONCLUSION: Ethnic differences exist in terms of antifibrotic HGF expression in lung fibroblasts derived from Caucasian and African American subjects. Reduced levels of HGF as well as a deficiency in c-Met receptor function appear to be present in African American patients with SSc. These findings may explain in part the greater disease severity and worse prognosis observed in African Americans with SSc.     

Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications

Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.     

长链非编码RNALOC728290在肝细胞癌患者肿瘤组织中的表达及意义

目的探讨肝细胞癌(hepatocellular carcinoma,HCC)患者肿瘤组织中长链非编码RNA(long non-coding RNA,Lnc RNA)LOC728290的表达及其临床意义。方法应用实时荧光定量PCR(real-time quantitative PCR,q RT-PCR)检测HCC患者手术切除的癌组织及其配对癌旁组织中Lnc RNA LOC728290的表达水平;统计分析其表达水平与患者临床病理特征之间的相关性,同时结合患者生存时间及预后随访情况,分析Lnc RNA LOC728290表达水平和无复发生存率之间的关系。结果 83%(54/65)HCC患者癌组织中Lnc RNA LOC728290的表达量较配对癌旁组织下调(P0.05);Lnc RNA LOC728290的表达水平在不同AFP水平、有/无微脉管浸润的患者中,呈显著差异表达(P0.05);生存分析表明Lnc RNA LOC728290表达水平低的HCC患者无复发生存率较其表达水平高的患者显著降低(P0.05)。结论 Lnc RNA LOC728290在HCC患者肿瘤组织中呈显著低表达,其有望成为临床HCC早期诊断、转移及预后评估的潜在分子标志物和治疗靶标。     

A potential cardioprotective role of hepatocyte growth factor in myocardial infarction in rats

OBJECTIVE: Cardiotrophic growth factors with anti-cell death actions on cardiac myocytes have gained attention for treatment of patients with myocardial infarction. Hepatocyte growth factor (HGF) plays a role in tissue repair and protection from injuries, however, the physiological role of HGF in the myocardium has not been well defined. We asked if HGF would afford to the infarcted myocardium. METHODS AND RESULTS: Mature cardiac myocytes prepared from adult rats expressed barely detectable levels of the c-Met/HGF receptor, however, c-Met receptor expression increased during cultivation, which meant that cardiac myocytes are potential targets of HGF. Addition of hydrogen peroxide remarkably decreased the number of viable mature cardiac myocytes in primary culture, whereas treatment with HGF enhanced survival of the cells subjected to the oxidant stress. Although very low levels of c-Met/HGF receptor and HGF mRNA expression were seen in normal rat hearts, both c-Met/HGF receptor and HGF mRNA levels rapidly increased to much higher levels than normal, when the rats were subjected to myocardial infarction. Immunohistochemical analysis of the c-Met receptor indicated that this receptor was expressed in cardiomyocytes localized in the border regions of the viable myocardium and in non-infarcted regions following myocardial infarction. CONCLUSION: The c-Met/HGF receptor is induced in cardiomyocytes following myocardial infarction and HGF exhibits protective effect on cardiomyocytes against oxidative stress. Our working hypothesis is that HGF may afford myocardial protection from myocardial infarction.     

血清肝细胞生长因子在慢性肝病中的意义

目的 肝细胞生长因子(HGF)能促进上皮细胞增生、运动、变形，是肝再生的起始因子之一，近来发现其在肝硬化和肝肿瘤的发生发展中也有重要作用。现主要探讨血清HGF水平在慢性肝病中的意义。方法 检测197例个体血清HGF水平，包括肝细胞癌(HCC)80例，肝硬化(LC)57例，慢性肝炎(CH)22例，正常对照38例。ELISA法检测血清HGF水平，并描绘受试者工作曲线(ROC)，确定HCC和LC患者HGF水平的最佳临界点。运用Spearman相关分析HGF水平和ALT、AST、GGT、白蛋白、总胆红索、凝血时间、肝癌大小、病理分级的相关性。结果 HCC、LC、CH和正常对照组的血清HGF中位值分别是6．767、151．200、7．017和3．476pg／m1。其中HCC组(P＜0．05)和比组(P＜0．01)的血清HGF水平显著高于正常对照组。LC组根据Child分级分层发现，Child C级患者的HGF水平明显高于Child A、B级。肝硬化ROC曲线显示，14pg／m1为临界值时效率最高。血清HGF水平仅发现与凝血时间有相关性(r=0．45，P＜0．01)。在HCC组中，未发现血清HGF水平与肿瘤大小、病理分级有任何相关。结论 血清中HGF水平增高与LC程度有关。     

Hyperbaric oxygenation promotes regeneration of biliary cells and improves cholestasis in rats

AIM:To investigate the effects of hyperbaric oxygenation(HBO) on regeneration of the biliary ductal system and postoperative cholestasis in hepatectomized rats.METHODS:HBO was performed in Wistar rats daily starting 12 h after a 70% partial hepatectomy.Regenerated liver weight,serum parameters and the proliferating cell nuclear antigen labeling index of hepatocytes and biliary ductal cells were measured.Hepatocyte growth factor(HGF),c-Met and transforming growth factor(TGF) β-1 mRNA expression levels were a...     

Expression of hepatocyte growth factor (HGF) and HGF receptor (c-met) proteins in liver diseases: an immunohistochemical study

BACKGROUND: Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes in vivo as well as in vitro. Serum levels of HGF vary in liver diseases, reflecting liver damage and dysfunction. However there are no studies reporting expression of HGF and HGF receptor (c-met protein) simultaneously in various liver diseases. METHODS: To clarify the clinical significance of HGF/c-met protein expression in liver diseases, liver tissues from 62 patients consisting of 7 with acute hepatitis (AH), 20 with chronic hepatitis (CH), 9 with liver cirrhosis (LC) and 26 with hepatocellular carcinoma (HCC) were immunohistochemically examined. RESULTS: Intense staining of HGF was observed in patients from AH, CH and LC, although no immunoreactivity was seen in HCC. The expression of c-met protein was higher in patients with HCC and AH than in those with CH (p < 0.05). A correlation of immunoreactivity between HGF and c-met protein was not observed expect in patients with LC (p < 0.01). The extent of c-met expression had no correlation with differentiation of HCC, tumour size, presence of portal invasion, or serum AFP levels. CONCLUSION: The results of the present study suggest that HGF plays an important role in human liver diseases, mostly in a manner independent of c-met protein expression.     

Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis

AIM: To study the in vitro and in vivo inhibitory effects of genistein on invasive potential of Bel 7402 hepatocellular carcinoma (HCC) cells and to explore the underlying mechanism. METHODS: Bel 7402 HCC cells were exposed to genistein. The invasive activity of tumor cells was assayed in transwell cell culture chamber. p125FAK expression and cell cycle were evaluated by a functional assay. Cell apoptosis analysis was performed with TUNEL method. In addition, bilateral subrenal capsule xenograft transplantation of HCC was performed in 10 nude mice. Genistein was injected and the invasion of HCC into the renal parenchyma was observed. Microvessels with immunohistochemical staining were detected. RESULTS: Genistein significantly inhibited the growth of Bel 7402 cells, the inhibitory rate of tumor cells was 26 -42%. The invasive potential of Bel 7402 cells in vitro was significantly inhibited, the inhibitory rate was 11-28%. Genistein caused G2/M cell cycle arrest, S phase decreased significantly. The occurrence of apoptosis in genistein group increased significantly. The expression of p125FAK in 5 μg/mL genistein group (15.26±0.16%) and 10 μg/mL genistein group (12.89±0.36%) was significantly lower than that in the control group (19.75±1.12%,P<0.05). Tumor growth in genistein-treated nude mice was significantly retarded in comparison to control mice, the inhibitory rate of tumor growth was about 20%. Genistein also significantly inhibited the invasion of Bel 7402 cells into the renal parenchyma of nude mice with xenograft transplant. The positive unit value of microvessels in genistein-treated group (10.422±0.807) was significantly lower than that in control group (22.330±5.696, P< 0.01). CONCLUSION: Genistein can effectively inhibit the invasive potential of Bel 7402 HCC cells by altering cell cycle, apoptosis and angiogenesis, inhibition of focal adhesion kinase may play a significant role in this process.