MDR1 gene expression in hepatocellular carcinoma and the peritumoral liver of patients with and without cirrhosis

Grudé, Pascale; Conti, Filomena; Mennecier, D; Louvel, A; Houssin, D; Weill, B; Calmus, Yvon

doi:10.1016/s0304-3835(02)00155-6

Cited by 35 publications

(25 citation statements)

References 12 publications

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“…HCC is one of the most frequent malignancies worldwide, and in addition it is extremely resistant to currently used chemotherapeutics [26]. We present here evidence demonstrating that Pgp, the protein encoded by the MDR1 gene, regulates the autocrine loop mediated by HGF/MET in P1(0.5) cells, leading to resistance to drug-mediated growth inhibition.…”

Section: Discussionmentioning

confidence: 81%

Down-regulation of the HGF/MET autocrine loop induced by celecoxib and mediated by P-gp in MDR-positive human hepatocellular carcinoma cell line

Mazzanti

Platini

Bottini

et al. 2009

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 33A c c e p t e d M a n u s c r i p t Graphical AbstractThe in vitro pro-autophagic, antiproliferative and pro-apoptotic effect of celecoxib on MDRpositive cells is mediated by the action of P-gp on the HGF/MET autocrine loop. small interfering RNA. These findings demonstrate that the constitutive expression of P-gp is involved in the HGF/MET autocrine loop that leads to increased expression of Bcl-2 and mTor, inhibition of eIF2α expression, resistance to autophagy/apoptosis and progression in the cell cycle.Since mTor inhibitors have been proposed in treatment of "drug resistant" cancer, these data may help explain the reversing effect of mTor inhibitors.

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Section: Discussionmentioning

confidence: 81%

Down-regulation of the HGF/MET autocrine loop induced by celecoxib and mediated by P-gp in MDR-positive human hepatocellular carcinoma cell line

Mazzanti

Platini

Bottini

et al. 2009

Biochemical Pharmacology

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“…9,18,19,21,23 This protein is also present in normal tissues, including the jejunum, liver, kidney, colon, and adrenal glands. 3,21,27 High levels of P-gp are expressed in tumor cells derived from organs normally expressing P-gp.…”

Section: Introductionmentioning

confidence: 99%

Cellular Characterization of Multidrug Resistance P-glycoprotein, Alpha Fetoprotein, and Neovascular Endothelium-Associated Antigens in Canine Hepatocellular Carcinoma and Cirrhotic Liver

et al. 2007

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Abstract. P-glycoprotein (P-gp), which is encoded by the multidrug resistance gene (MDR-1); alpha fetoprotein (AFP); and vascular endothelium-associated antigens are well-known markers for human and canine hepatic diseases. We obtained liver tissues from 5 dogs with hepatocellular carcinoma (HCC) and 12 dogs with cirrhosis, and we performed histopathologic and immunohistochemical evaluations using anti-P-gp, anti-AFP, anti-CD31, and anti-CD34 antibodies. P-gp was expressed at higher levels in HCC than in cirrhotic livers (P , .01), and was most commonly localized in biliary canaliculi and small ductuli. AFP was localized mainly in the cytoplasm in HCC (P , .01) and in a few cases of cirrhosis. In both HCC and cirrhosis, the AFP-positive cells were morphologically similar to normal hepatocytes and showed an even cytoplasmic distribution of AFP. The endothelial markers CD31 and CD34 were used to investigate vascular distribution. CD31 was expressed strongly in the portal area and parenchyma in HCC, but it was rarely observed in the parenchyma in cirrhosis. CD34 expression could not be detected in both HCC and cirrhosis. This study constitutes the first comprehensive study of P-gp, AFP, and endothelial markers in canine HCC and cirrhosis. The importance of these markers in HCC and cirrhosis in dogs was demonstrated and provides a more accurate basis for a definitive diagnosis of HCC and cirrhosis in dogs.

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“…But almost all MDR reverse studies are only performed in vitro [3][4][5] , and few are performed in vivo. A study [6] indicates that overexpression of Pgp, a product of MDR1, is intimately associated with liver cancer development and therefore inhibitors of Pgp should inhibit the development of liver cancer. Accordingly, we determined the effect of bromocriptine (BCT), a potent inhibitor of Pgp [7,8] , and tumor necrosis factor-a (TNF-α) [9][10][11] which could downregulate expression of the MDR-associated genes LRP and MRP in multidrug resistant model of nude mice via orthotopic implantation of multidrug resistant human hepatocellular carcinoma (HCC) cells HepG 2 /adriamycin (ADM).…”

Section: Introduction Introduction Introduction Introduction Introducmentioning

confidence: 99%

Synergistic effect of bromocriptine and tumor necrosis factor-α on reversing hepatocellular carcinoma multidrug resistance in nude mouse MDR1 model of liver neoplasm

Ding

Chen²,

Zhang³

et al. 2005

WJG

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Abstract Abstract Abstract AIM:To investigate the effect of bromocriptine (BCT) and tumor necrosis factor-α (TNF-α) on hepatocellular carcinoma (HCC) multidrug resistance (MDR) in nude mouse MDR model of liver neoplasm. METHODS:Human hepatocarcinoma cell line HepG 2 , drug resistant hepatocarcinoma cell line HepG 2 /adriamycin (ADM) and hepatocarcinoma cell line transfected with TNF-α gene HepG 2 /ADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established (HepG 2 , ADM, TNF, BCT groups). Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor histological character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins (MRP, LRP) of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay. RESULTS:The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group (67%) compared to ADM and TNF groups, and similar to HepG 2 group (54%). MDR1 and LRPmRNA could be detected in all groups, but TNF-α was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG 2 group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay.

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MDR1 gene expression in hepatocellular carcinoma and the peritumoral liver of patients with and without cirrhosis

Cited by 35 publications

References 12 publications

Down-regulation of the HGF/MET autocrine loop induced by celecoxib and mediated by P-gp in MDR-positive human hepatocellular carcinoma cell line

Down-regulation of the HGF/MET autocrine loop induced by celecoxib and mediated by P-gp in MDR-positive human hepatocellular carcinoma cell line

Cellular Characterization of Multidrug Resistance P-glycoprotein, Alpha Fetoprotein, and Neovascular Endothelium-Associated Antigens in Canine Hepatocellular Carcinoma and Cirrhotic Liver

Synergistic effect of bromocriptine and tumor necrosis factor-α on reversing hepatocellular carcinoma multidrug resistance in nude mouse MDR1 model of liver neoplasm

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