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Pien Tze Huang Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells by Repressing PDGFRB/YAP/CCN2 Axis Activity

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Chinese Journal of Integrative medicine 2024年第2期30卷 115-124页

作者： LUO Zhi-yi TIAN Qi CHENG Niang-mei LIU Wen-han YANG Ye CHEN Wei ZHANG Xiang-zhi ZHENG Xiao-yuan CHEN Ming-sheng ZHUANG Qiu-yu ZHAO Bi-xing LIU Cong-sheng LIU Xiao-long LI Qin WANG Ying-chao The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China fujian Pien Tze Huang Enterprise Key Laboratory of Natural medicine Research and Development Zhangzhou Pien Tze Huang Pharmaceutical Co.Ltd.ZhangzhouFujian Province(363099)China College of Biological Science and Engineering and Mengchao med-X Center Fuzhou UniversityFuzhou(350116)China Department of Internal medicine Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou(350025)China

Objective:To investigate the effects of Pien Tze Huang(PZH) on the migration and invasion of HCC cells and underlying molecular ***:Cell counting kit-8(CCK-8) was applied to evaluate the cell viabilities of SMMC-7721,SK-Hep-1,C3A and HL-7702(6 × 10^(3)cells/well) co-incubated with different concentrations of PZH(0,0.2,0.4,0.6,0.8 mg/mL) for 24 ***,wound healing assay,CCK-8and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration,invasion,proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells(650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells),*** vivo,lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of ***-Hep-1 cells(10^(6)cells/200 μL per mice) were injected into B-NDG mice via tail *** 8 mice were randomly divided into PZH and control groups,4 mice in each *** 2-d inoculation,mice in the PZH group were administered with PZH(250 mg/kg,daily) and mice in the control group received only vehicle(PBS) from the 2nd day after xenograft to day *** analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of *** real-time polymerase chain reaction(qRT-PCR) and Western blot were applied to verify RNA-seq *** reporter assay was performed to examine the transcriptional activity of yes-associated protein(YAP).Results:PZH treatment significantly inhibited the migration,invasion,proliferation and promoted the apoptosis of HCC cells in vitro and in vivo(P<0.01).Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of *** study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta(PDGFRB),YAP,connective tissue growth factor(CCN2),N-cadherin,vimentin and matrix metallopeptidase 2(MMP2,P<0.01).Meanwhile,the phosphorylatio

关键词： PienTzeHuang hepatocellular carcinoma RNA-seq Hippo yes-associated protein

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TROVE2 regulated invasion and migration of hepatocellular carcinoma cells via heparanase

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Oncology and Translational medicine 2024年第2期10卷 66-72页

作者： Niangmei Cheng Xiaoyuan Zheng Jingyun Huang FeiWang Yang Wang Yue Zhong Yingchao Wang Gaoxiong Wang Bixing Zhao The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou 350025P.R.China Mengchao med-X Center Fuzhou UniversityFuzhou 350116P.R.China Department of Surgery Quanzhou Maternity and Children's Hospital700 Fengze StreetQuanzhouFujianChina Department of General Surgery the Second AffiliatedHospitalFujian Medical UniversityQuanzhouFujianChina

Background:The role of TROVE domain family member 2(TROVE2)has been well-demonstrated in autoimmune diseases;however,its involvement in liver cancer remains ***,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 *** impact of TROVE2 on migration and invasion in HCC cells was analyzed through Transwell assays and Western ***-throughput transcriptome sequencing and bioinformatics analyses were performed to identify downstream target ***-complementation experiments were employed to verify the influence of downstream proteins on TROVE2-induced invasion and migration of HCC ***:TROVE2 exhibited significant overexpression in liver cancer tissue,correlating with shorter overall *** 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 *** sequencing and bioinformatics analysis identified heparanase(HPSE)as a downstreamtarget protein of *** back-complementation experiments provided evidence that HPSE overexpression promoted TROVE2-mediated prometastasis ***,the study revealed that TROVE2 was capable of regulating the EMT pathway through GSK-3β***: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.

关键词： Epithelial-mesenchymal transition(EMT) Heparanase(HPSE) Hepatocellular carcinoma(HCC) TROVE2

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Effect of miR-130a targeting phosphase and tensin homology deleted on chromosome ten/ phosphoinositol 3 kinase/protein kinase B axis on apoptosis of renal tissue cells in rats with diabetic kidney disease

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China medical Abstracts(Internal medicine) 2024年第2期41卷 94-94页

作者：许春梅 Dept Nephrol Longyan 1st HospFujian Med UnivLongyan 364000

Objective To investigate the effect of miR-130a targeting phosphase and tensin homology deleted on chromosome ten(PTEN)/phosphoinositide 3 kinase(PI3K)/protein kinase B(AKT)pathway on renal tissue cell apoptosis in diabetic kidney disease(DKD)*** The DKD rat model was constructed by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).72 rats were divided into normal control group(NC),DKD model group(DKD),miR-13Oa agonist negative control group(NC agomir),and miR-130a agonist group(miR-130a agomir),miR-130a agomir+PTEN overexpression negative control group(miR-13a agomir+pcDNA),and miR-130a agomir+PCDNA-PTEN over-expression group(miR-130a Agomir+PCDNA-PTEN),with 12 rats in each *** microalbumin kit was used to detect 24 h urine albumin(UAlb).Fasting blood glucose(FBG),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected by automatic biochemical *** changes of renal tissue were detected by HE *** levels of serum IL-6 and TNF-αwere detected by *** apoptosis of renal tissue was detected by TUNEL *** expression of miR-130a was detected by qRT-PCR,and the expression of B-cell lymphoma-2-associated X protein(Bax).

关键词： miR rats kidney

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Color Doppler velocity profile and contrast-enhanced ultrasonography in assessment of liver cirrhosis

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Hepatobiliary & Pancreatic Diseases International 2008年第1期7卷 34-39页

作者： Lin, Li-Wu Duan, Xue-Jun Wang, Xiao-Yan Xue, En-Sheng He, Yi-Mi Gao, Shang-Da Yu, Li-Yun fujian med univ Union Hosp Fujian Dept Ultrasound Fuzhou 350001 Peoples R China

BACKGROUND: This study was designed to probe the clinical value in assessing the degree of liver cirrhosis by using the arrival time of contrast agent in the right portal vein in contrast-enhanced ultrasonography, as well as the velocity and flow volume in the right portal vein using the color Doppler velocity profile technique. METHODS: Twenty-eight patients with HBV post-hepatic cirrhosis were grouped into compensated (13 patients) and decompensated cirrhosis (15); 30 patients without hepatic cirrhosis served as controls. Written informed consent was obtained from each patient. All the patients with hepatic cirrhosis were pathologically confirmed by percutaneous biopsy. SonoVue was injected to detect the arrival time in the right portal vein. The velocity and flow volume in the right portal vein were measured. The value of each parameter was compared for correlation analysis. RESULTS: The arrival time in the right portal vein in the cirrhosis group was much longer than that in the control group (24.92 +/- 1.34 vs. 20.81 +/- 0.55 sec, respectively, P<0.01). The mean velocity, maximal velocity and flow volume in the cirrhosis group were much lower than those in the control group (10.64 +/- 0.84 vs. 14.78 +/- 0.71 cm/sec, 13.68 +/- 1.02 vs. 17.30 +/- 0.68 cm/sec and 358.72 +/- 23.63 vs. 438.61 +/- 16.86 ml/min, respectively, P<0.01). With the development of cirrhosis, the arrival time in the right portal vein was longer (P<0.05), and the velocity and flow volume was lower (P<0.01). There was a negative correlation between arrival time and mean velocity, maximal velocity and flow volume in the right portal vein in the cirrhosis group (r=-0.547, P<0.01; r=-0.508, P<0.05; r=-0.471, P<0.05, respectively). CONCLUSIONS: With the development of liver cirrhosis, the arrival time of contrast agent in the right portal vein is gradually prolonged, whereas the velocity and flow volume in this vein decreases markedly, and there is a negative correlation between the results of the

关键词： liver cirrhosis portal vein contrast media hemodynamic phenomena

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Ammonia metabolism capacity of HepG2 cells with high expression of human glutamine synthetase

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Hepatobiliary & Pancreatic Diseases International 2008年第6期7卷 621-627页

作者： Tang, Nan-Hong Wang, Xiao-Qian Li, Xiu-Jin Chen, Yan-Ling fujian med univ Union Hosp Hepatobiliary Surg Inst Fujian Prov Fuzhou 350001 Peoples R China

BACKGROUND: Currently, one of the tough problems for the application of bioartificial liver (BAL) is the shortage of suitable hepatocytes. There are reports on different types of BAL assistance developed with porcine hepatocytes and HepG2 C3A cells, but their defects are obvious. In recent years, some studies focus more on liver cells with features of human origin and improved detoxification. In this study, a hepatocyte line with high expression of human glutamine synthetase (hGS) was raised and its capacity for ammonia metabolism was investigated. METHODS: hGS cDNA and alpha-fetoprotein transcription regulatory element (AFP-TRE) were cloned with the designed primers. The eukaryotic expression vectors, pLNChGS and pLNAFhGS, were constructed and transfected into PA317 cells. Recombinant retroviruses (Retro-hGS and Retro-AFhGS) were produced and then infected into HepG2 cells. G418-resistant cell clones, HepG2/pLNChGS and HepG2/pLNAFhGS, were selected and amplified. Then hGS mRNA was measured by semi-quantitative RT-PCR; hGS enzymatic activity and ammonia metabolism analysis in different concentration of NH(4)(+) were detected with a quantitative biochemistry kit. The cell proliferation was also detected by MTT chromatometry. RESULTS: The expression of hGS mRNA in HepG2/pLNChGS cells (8.306+/-0.336) and HepG2/pLNAFhGS cells (21.358+/-1.716) was much stronger than in control cells (P<0.05), and that in HepG2/pLNAFhGS cells was markedly stronger than in HepG2/pLNChGS cells (P<0.05). The hGS enzymatic activities of HepG2/pLNChGS cells (3.279+/-0.328 U/mg prot) and HepG2/pLNAFhGS cells (4.557+/-0.253 U/mg prot) were higher than those of control cells (P<0.05), and those of HepG2/ pLNAFhGS cells were also higher than the activities of HepG2/pLNChGS cells (P<0.05). In addition, the effect of hGS introduction on HepG2 cell proliferation was not significant. The amount of glutamine synthesis in HepG2/pLNChGS or HepG2/pLNAFhGS cells in three different concentrations of NH(4)(+

关键词： hepatocytes glutamine synthetase, human ammonia detoxification

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Multisite mutations of the PRSS1 gene in a Chinese patient with chronic pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2008年第3期7卷 331-332页

作者： Liu, Qi-Cai Gao, Feng Cheng, Zu-Jian Ou, Qi-Shui fujian med univ Dept Lab Med Affiliated Hosp 1 Fuzhou 350005 Peoples R China fujian med univ Dept Pathol Affiliated Hosp 1 Fuzhou 350005 Peoples R China

BACKGROUND: Chronic pancreatitis shows alterations in the trypsinogen gene (protease serine 1, PRSS1) in some individuals. The conversion of trypsinogen to trypsin in the pancreas is believed to be one of the causes of pancreatitis. This study was to identify the mutation of the PRSS1 gene in a Chinese patient with chronic pancreatitis and to analyze the clinical features of the disease. METHODS: In 6 patients with chronic pancreatitis and 120 normal controls, PRSS1 genes were amplified by the polymerase chain reaction and the products were analyzed by sequencing. RESULTS: Multisite mutations of PRSS1 were found in a patient with chronic pancreatitis. C to A mutation occurred in exon 3 of PRSS1, and T to A mutation in the same exon. These mutations were not found in normal controls or the patients with chronic pancreatitis. CONCLUSION: These are novel mutations in PRSS1.

关键词： chronic pancreatitis PRSS1 multisite mutation

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Effect of fatty liver background on contrast-enhanced ultrasonographic appearance of focal nodular hyperplasia

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Hepatobiliary & Pancreatic Diseases International 2007年第6期6卷 610-615页

作者： Lin, Li-Wu Yang, Jia-Jia Lin, Xue-Ying Xue, En-Sheng He, Yi-Mi Gao, Shang-Da Yang, Long Yu, Li-Yun fujian med univ Union Hosp Dept Ultrasound Fuzhou 350001 Peoples R China

BACKGROUND: Focal nodular hyperplasia (FNH) is increasingly diagnosed as a result of the advances in imaging studies such as contrast-enhanced ultrasonography (CEUS), enhanced computed tomography and magnetic resonance imaging. However, FNH with atypical features can be difficult to differentiate from other benign and malignant tumors. The aim of this study was to investigate the influence of fatty liver background on the CEUS characteristics of FNH. METHODS: Twenty-six patients with FNH were divided into two groups: group A included 14 patients with fatty liver and group B included 12 patients with normal liver background. Conventional two-dimensional ultrasonography and color Doppler flow imaging (CDFI) were conducted and followed by real-time dual-frame CEUS. RESULTS: On two-dimensional ultrasonography, hypoechoic nodules were present in most of the patients in group A (12/14) and hyperechoic nodules in most of those in group B (7/12). The difference in the nodule echotextures between the two groups was statistically significant (P0.05). On CEUS, nodules with a central spoked-wheel-like enhancement pattern in the early arterial phase were observed in 8 patients in group A and those with an eccentric enhancement pattern in the remaining 6 patients. In this group, 3 patients had hypoechoic nodules in the delayed phase. Eleven of the 14 patients in this group were diagnosed accurately with CEUS. In group B, nodules with a rapid central spoked-wheel-like enhancement pattern in the early arterial phase were found in 8 patients by CEUS and those with rapid an eccentric enhancement pattern in 4. The nodules were found to be continuously enhanced in the delayed phase. All of the patients in group B were accurately diagnosed with CEUS. CONCLUSIONS: A FNH nodule on a background of fatty liver may present a hypoechoic pattern on two-dimensi

关键词： ultrasonography contrast media focal nodular hyperplasia fatty liver

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Ultrasonographic diagnosis of hepatic fungal infection

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Hepatobiliary & Pancreatic Diseases International 2008年第2期7卷 169-173页

作者： Yang, Jia-Jia Lin, Li-Wu Lin, Zheng-Hu Xue, En-Sheng Gao, Shang-Da He, Yi-Mi fujian med univ Dept Ultrasound Union Hosp Fuzhou 350001 Peoples R China

BACKGROUND: Hepatic fungal infection is difficult to diagnose early because of the lack of related clinical knowledge. In this study, we analyzed the ultrasonic manifestations of hepatic fungal infection, in order to determine the diagnostic value of ultrasonography. METHODS: In 8 patients with hepatic fungal infection, the results of color Doppler flow images (CDFI) and contrast-enhanced ultrasonography (CEUS) were compared with those of ultrasound-guided biopsy. RESULTS: In the 8 patients with pathologically proven hepatic fungal infection, 5 showed multiple hypoechoic lesions with unequal sizes in the liver, commonly less than 2 cm in diameter. Some of the hypoechoic lesions showed a hyperechoic strip in the periphery, while a minority showed a 'bull's eye' pattern, which is considered a typical manifestation of metastatic hepatic carcinoma. Solitary lesions in the right lobe of the liver were found in the other 3 patients. No blood flow signals were found in any lesions with CDFI. In the lesions a 'filling defect' pattern was shown by CEUS, indicating no enhancement in the arterial phase, the portal vein phase and the delayed phase, except for 3 patients, in whom the lesions were slightly enhanced in the periphery during the early arterial phase. CONCLUSIONS: Hepatic fungal infection is characterized by an ultrasonic manifestation of multiple hypoechoic lesions with inequal size. A small number of lesions may show a characteristic 'bull's eye' appearance. Moreover, a 'filling defect' pattern on CEUS is helpful to make a correct diagnosis. In addition, ultrasound-guided biopsy is an important method for accurate diagnosis of hepatic fungal infection.

关键词： ultrasonography liver diseases mycoses

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Antisense RhoC gene suppresses proliferation and invasion capacity of human QBC939 cholangiocarcinoma cells

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Hepatobiliary & Pancreatic Diseases International 2007年第5期6卷 516-520页

作者： Shi, Zheng Chen, Ming-Liu He, Qing-Liang Zeng, Jin-Hua fujian med univ Dept Gen Surg Affiliated Hosp 1 Fuzhou 350005 Peoples R China

BACKGROUND: Cholangiocarcinoma is a highly aggressive, fatal malignancy, which is resistant to all current therapeutic approaches. The recent elevation in the incidence of cholangiocarcinoma has highlighted the need for novel approaches targeting the molecular basis of its invasiveness. Previously we reconstructed a RhoC antisense eukaryotic expression vector and transfected it into a cholangiocarcinoma cell line (QBC939) by the lipofectamine method. This study was undertaken to determine the effect of the antisense RhoC gene on the proliferation and invasion capacity of QBC939. METHODS: Antisense RhoC cDNA was transfected into QBC939 with lipofectin 2000. The cell growth curve was constructed to determine the proliferation rate of cells; flow cytometry was used to analyze cell cycle changes of the tumor cells; and a Boyden chamber was used to assess the invasive ability of the cells before and after gene transfection. RESULTS: After the antisense RhoC cDNA was transfected, the number of colonies formed was significantly lower than that in the other two groups (54 +/- 8 vs. 91 +/- 11 vs. 90 +/- 9, P<0.05) so was the number of the cells which crossed to the lower surface of the matrigel-coater filters (36 +/- 6 vs. 96 +/- 12 vs. 95 +/- 7, P<0.05). There was also a higher percentage of transfected cells in G1 phase than in the other two groups (52.5% vs. 43.4% vs. 43.7%). CONCLUSION: The antisense RhoC gene can suppress the capacities of proliferation and invasion in a cholangiocarcinoma cell line in vitro.

关键词： RhoC gene cholangiocarcinorna transfection invasion gene therapy

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Interstitial chemotherapy with ricin-loaded thermosensitive hydrogel in pancreatic cancer xenograft

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Hepatobiliary & Pancreatic Diseases International 2009年第4期8卷 418-423页

作者： Chen, Zhi-Kui Lin, Li-Wu Weng, Xiu-Hua Xue, En-Sheng Lin, Yong-Hua fujian med univ Union Hosp Dept Ultrasound Fuzhou 350001 Peoples R China fujian med univ Affiliated Hosp 1 Dept Pharm Fuzhou 350001 Peoples R China Fuzhou Gen Hosp Dept Gen Surg Fuzhou 350025 Peoples R China

BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies, and has a poor prognosis. Despite efforts made in multiple fields, there has been little success in improving the disease-free survival rate of patients. This study was undertaken to investigate the effectiveness and feasibility of using intra-tumoral injection of ricin-loaded thermosensitive hydrogel for treatment of pancreatic cancer xenografts, attempting to develop a new treatment for human pancreatic cancer. METHODS: BALB/c-(nu/nu) nude mice were inoculated subcutaneously in the right flank with the human pancreatic cancer cells, SW1990. Fourteen days after inoculation, 32 mice, bearing tumors of volume 1.5-2.0 cm(3), were randomly assigned to one of four groups, and given an intra-tumoral injection of: (1) saline; (2) 23% w/w thermosensitive hydrogel alone; (3) ricin, 10 mu g/kg; or (4) 10 mu g/kg ricin loaded in thermosensitive hydrogel. On day 14 after administration, the tumors were excised to calculate the inhibition rate of tumor growth and perform histopathological examination. Tumor cell apoptosis was detected by flow cytometry, and RT-PCR was performed to evaluate the mRNA expression levels of Bc12 and Bax. RESULTS: Intra-tumoral injection of ricin-loaded thermosensitive hydrogel resulted in remarkable control of tumor growth. The tumor became necrotic by day 14 after administration. The histological results clearly confirmed that the tumor cells were lysed. The percentage of apoptotic cells detected by flow cytometry was higher in the ricin hydrogel group than in the other groups. Semi-quantitative RT-PCR revealed that the mRNA expression level of Bc12 was down-regulated whereas Bax was upregulated. CONCLUSIONS: Intra-tumoral injection of ricin-loaded thermosensitive hydrogel may provide an effective approach for interstitial chemotherapy in pancreatic cancer. Inducing apoptosis by downregulating Bcl2 expression and upregulating Bax expression may be a key molecular mechanism.

关键词： pancreatic neoplasm ricin hydrogel therapeutics drug delivery system

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