TFPI‐2 Downregulates Multidrug Resistance Protein in 5‐FU‐Resistant Human Hepatocellular Carcinoma BEL‐7402/5‐FU Cells

Lü, Fei; Hou, Yongzhong; Song, Ying; Yuan, Zhengjiang

doi:10.1002/ar.22611

Cited by 16 publications

(9 citation statements)

References 22 publications

(22 reference statements)

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“…Human HCC cell lines — SMMC-7721, HepG2, Huh7, Hep3B, MHCC97H, HCCLM3 and Bel-7402 — were purchased from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Science. Drug resistant cell lines — Bel-7402/5-Fludrouracil (5-FU) and Bel-7402/Adriamycin (ADM) — were obtained by exposing Bel-7402 to stepwise increases in 5-FU or ADM according to reported methods [ 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

Nestin overexpression in hepatocellular carcinoma associates with epithelial-mesenchymal transition and chemoresistance

Zhang

Zeng

et al. 2016

J Exp Clin Cancer Res

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BackgroundNestin expression has been reported to be associated with the prognosis of many solid tumors including human hepatocellular carcinoma (HCC). The present study aimed to identify the role, if any, of Nestin in the chemotherapeutic treatment of HCC.MethodsWe determined Nestin expression in nine HCC cell lines and 220 tissue samples of advanced HCC patients (retrospectively registered) treated with FOLFOX regimens. We examined the correlations between Nestin expression and clinicopatholgical variables and HCC prognosis. Also, we used in vitro and in vivo methods to determine the effects of Nestin expression on HCC cell invasion, migration and chemosensitivity.ResultsNestin expression was significantly increased in HCC tissues and drug-resistant cell lines, and the presence of high levels of Nestin was associated with poor survival. We also showed that drug-resistance occurred in HCC cells with epithelial-mesenchymal transition (EMT), which in turn enhanced invasion ability. Nestin depletion reversed drug-resistance in the Bel-7402/5-FU and Bel-7402/ADM cell lines. Nestin knockdown enhanced chemotherapeutic efficacy in nude mice. Moreover, Nestin up-regulation in Bel-7402 was associated with the activation of Wnt/β-catenin signaling.ConclusionOur findings suggest that Nestin inhibitors may be useful for the chemotherapy of HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0387-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Nestin overexpression in hepatocellular carcinoma associates with epithelial-mesenchymal transition and chemoresistance

Zhang

Zeng

et al. 2016

J Exp Clin Cancer Res

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“…The PI3K inhibitor LY294002, the p38 MAPK inhibitor SB203580, and the JNK inhibitor SP600125 were tested and did not affect P-glycoprotein expression [25]. Various reports have described the association between p38 MAPK and P-glycoprotein: the activation of p38 MAPK reduced the expression of MDR1 and MRP1 mRNAs in 5fluorouracil-resistant BEL-7402/5-FU cells [29], whereas the inhibition of p38 MAPK reduced the activator protein-1 (AP-1) activity and MDR1 gene expression in vincristineresistant SGC7901/VCR cells [30]. SB203580 also reversed the P-glycoprotein-mediated MDR of L1210/VCR cells without affecting P-glycoprotein expression [31].…”

Section: Modulation Of P-glycoprotein Expression By the Mitogen-mentioning

confidence: 99%

Regulations of P-Glycoprotein/ABCB1/MDR1in Human Cancer Cells

Katayama

Noguchi

Sugimoto

2014

New Journal of Science

106

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Multidrug resistance (MDR) in cancer cells is a phenotype whereby cells display reduced sensitivity to anticancer drugs, based on a variety of mechanisms, including an increase in drug efflux, the reduction of drug uptake, the activation of cell growth and survival signaling, the promotion of DNA repair, and the inhibition of apoptosis signaling. Increased expression of the plasma membrane drug efflux pumps, the ATP-binding cassette (ABC) transporters, is involved in MDR. P-Glycoprotein/ABCB1 is a member of the ABC transporter family, and facilitates the efflux of various anticancer drugs, including anthracyclines,vincaalkaloids, epipodophyllotoxins, taxanes, and kinase inhibitors, from cells. P-Glycoprotein is also expressed in normal tissues and cells, including the kidney, liver, colon, and adrenal gland, to transport and/or secrete substrates and at the blood-brain, blood-placenta, and blood-testis barriers to protect these tissues from toxic substances. To understand the mechanistic functions of P-glycoprotein and to overcome MDR, investigators have identified the substrates and competitive inhibitors of P-glycoprotein. Recently, we and other groups reported associations between cellular signaling pathways and the expression, stability, degradation, localization, and activity of P-glycoprotein. The present review summarizes the currently available information about the transcriptional and posttranslational regulation of P-glycoprotein expression and function.

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“…Overexpression of TFPI-2 could inhibit cell migration 24 , proliferation 25 , and promote cell apoptosis 26 in glioma cells. Moreover, TFPI-2 inhibits the function of P-glycoprotein efflux pump, resulting in reduced TMZ efflux in GB cells 27 . However, whether TFPI-2 is the potential target of lncRNA AC003092.1 in TMZ-resistant GB remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA AC003092.1 promotes temozolomide chemosensitivity through miR-195/TFPI-2 signaling modulation in glioblastoma

Xu¹,

Liu²,

Lian³

et al. 2018

Cell Death Dis

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Temozolomide (TMZ) and radiation therapy combination for glioblastoma (GB) patients has been considered as the most effective therapy after surgical procedure. However, the overall clinical prognosis remains unsatisfactory due to intrinsic or developing resistance to TMZ. Recently, increasing evidence suggested that long noncoding RNAs (lncRNAs) play a critical role in various biological processes of tumors, and have been implicated in resistance to various drugs. However, the role of lncRNAs in TMZ resistance is poorly understood. Here, we found that the expression of lncRNA AC003092.1 was markedly decreased in TMZ resistance (TR) of GB cells (U87TR and U251TR) compared with their parental cells (U87 and U251). In patients with glioma, low levels of lncRNA AC003092.1 were correlated with increased TMZ resistance, higher risk of relapse, and poor prognosis. Overexpression of lncRNA AC003092.1 enhances TMZ sensitivity, facilitates cell apoptosis, and inhibits cell proliferation in TMZ-resistant GB cells. In addition, we identified that lncRNA AC003092.1 regulates TMZ chemosensitivity through TFPI-2-mediated cell apoptosis in vitro and in vivo. Mechanistically, further investigation revealed that lncRNA AC003092.1 regulates TFPI-2 expression through miR-195 in GB. Taken together, these data suggest that lncRNA AC003092.1 could inhibit the function of miR-195 by acting as an endogenous CeRNA, leading to increased expression of TFPI-2; this promotes TMZ-induced apoptosis, thereby making GB cells more sensitive to TMZ. Our findings indicate that overexpression of lncRNA AC003092.1 may be a potential therapy to overcome TMZ resistance in GB patients.

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TFPI‐2 Downregulates Multidrug Resistance Protein in 5‐FU‐Resistant Human Hepatocellular Carcinoma BEL‐7402/5‐FU Cells

Cited by 16 publications

References 22 publications

Nestin overexpression in hepatocellular carcinoma associates with epithelial-mesenchymal transition and chemoresistance

Nestin overexpression in hepatocellular carcinoma associates with epithelial-mesenchymal transition and chemoresistance

Regulations of P-Glycoprotein/ABCB1/MDR1in Human Cancer Cells

Long noncoding RNA AC003092.1 promotes temozolomide chemosensitivity through miR-195/TFPI-2 signaling modulation in glioblastoma

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