• 제목/요약/키워드: Hepatocellular carcinoma cells

검색결과 311건 처리시간 0.022초

DN200434, an orally available inverse agonist of estrogen-related receptor γ, induces ferroptosis in sorafenib-resistant hepatocellular carcinoma

  • Dong-Ho, Kim;Mi-Jin, Kim;Na-Young, Kim;Seunghyeong, Lee;Jun-Kyu, Byun;Jae Won, Yun;Jaebon, Lee;Jonghwa, Jin;Jina, Kim;Jungwook, Chin;Sung Jin, Cho;In-Kyu, Lee;Yeon-Kyung, Choi;Keun-Gyu, Park
    • BMB Reports
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    • 제55권11호
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    • pp.547-552
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    • 2022
  • Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.

Downregulation of SETD5 Suppresses the Tumorigenicity of Hepatocellular Carcinoma Cells

  • Park, Mijin;Moon, Byul;Kim, Jong-Hwan;Park, Seung-Jin;Kim, Seon-Kyu;Park, Kihyun;Kim, Jaehoon;Kim, Seon-Young;Kim, Jeong-Hoon;Kim, Jung-Ae
    • Molecules and Cells
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    • 제45권8호
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    • pp.550-563
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    • 2022
  • Hepatocellular carcinoma (HCC) is an aggressive and incurable cancer. Although understanding of the molecular pathogenesis of HCC has greatly advanced, therapeutic options for the disease remain limited. In this study, we demonstrated that SETD5 expression is positively associated with poor prognosis of HCC and that SETD5 depletion decreased HCC cell proliferation and invasion while inducing cell death. Transcriptome analysis revealed that SETD5 loss downregulated the interferon-mediated inflammatory response in HCC cells. In addition, SETD5 depletion downregulated the expression of a critical glycolysis gene, PKM (pyruvate kinase M1/2), and decreased glycolysis activity in HCC cells. Finally, SETD5 knockdown inhibited tumor growth in xenograft mouse models. These results collectively suggest that SETD5 is involved in the tumorigenic features of HCC cells and that targeting SETD5 may suppress HCC progression.

Effect of Paclitaxel-loaded Nanoparticles on the Viability of Human Hepatocellular Carcinoma HepG2 Cells

  • Hou, Zhi-Hong;Zhao, Wen-Cui;Zhang, Qi;Zheng, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권5호
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    • pp.1725-1728
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    • 2015
  • Objective: To explore effects of paclitaxel-loaded poly lactic-co-glycolic acid (PLGA) particles on the viability of human hepatocellular carcinoma (HCC) HepG2 cells. Materials and Methods: The viability of HepG2 cells was assessed using MTT under different concentrations of prepared paclitaxel-loaded particles and paclitaxel (6.25, 12.5, 25, 50, and 100 mg/L), and apoptosis was analyzed using Hochest33342/Annexin V-FITC/PI combined with an IN Cell Analyzer 2000. Results: Paxlitaxel-loaded nanoparticles were characterized by narrow particle size distribution (158.6 nm average particle size). The survival rate of HepG2 cells exposed to paclitaxel-loaded PLGA particles decreased with the increase of concentration and time period (P<0.01 or P<0.05), the dose- and time-dependence indicating sustained release (P<0.05). Moreover, apoptosis of HepG2 cells was induced, again with an obvious dose- and time-effect relationship (P<0.05). Conclusions: Paclitaxel-loaded PLGA particles can inhibit the proliferation and induce the apoptosis of HCC HepG2 cells. This new-type of paclitaxel carrier body is easily made and has low cost, good nanoparticle characterization and sustained release. Hence, paclitaxel-loaded PLGA particles deserve to be widely popularized in the clinic.

Drug Resistance Effects of Ribosomal Protein L24 Overexpression in Hepatocellular Carcinoma HepG2 Cells

  • Guo, Yong-Li;Kong, Qing-Sheng;Liu, Hong-Sheng;Tan, Wen-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권22호
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    • pp.9853-9857
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    • 2014
  • Background: The morbidity and mortality rate of liver cancer continues to rise in China and advanced cases respond poorly to chemotherapy. Ribosomal protein L24 has been reported to be a potential therapeutic target whose depletion or acetylation inhibits polysome assembly and cell growth of cancer. Materials and Methods: Total RNA of cultured amycin-resistant and susceptible HepG2 cells was isolated, and real time quantitative RT-PCR were used to indicate differences between amycin-resistant and susceptible strains of HepG2 cells. Viability assays were used to determine amycin resistance in RPL24 transfected and control vector and null-transfected HepG2 cell lines. Results: The ribosomal protein L24 transcription level was 7.7 times higher in the drug-resistant HepG2 cells as compared to susceptible cells on quantitative RT-PCR analysis. This was associated with enhanced drug resistance as determined by methyl tritiated thymidine (3H-TdR) incorporation. Conclusions: The ribosomal protein L24 gene may have effects on drug resistance mechanisms in hepatocellular carcinoma HepG2 cells.

The Inhibitory Effect of NLRP3 Deficiency in Hepatocellular Carcinoma SK-Hep1 Cells

  • Choi, Wonhyeok;Cho, Hyosun
    • 한국미생물·생명공학회지
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    • 제49권4호
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    • pp.594-602
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    • 2021
  • The NLRP3 (nucleotide-binding domain, leucine-rich repeat family pyrin domain containing 3) inflammasome plays an important role in the initiation of inflammatory responses, through the recognition of pathogen-associated molecular patterns and tumor progression, including tumor growth and metastasis. In this study, we examined the effects of defective NLRP3 on the growth, migration, and invasiveness of hepatocellular carcinoma (HCC) SK-Hep1 cell. First, HCC SK-Hep1 cells were transfected with human NLRP3 targeting LentiCRISPRv2 vector using the CRISPR-Cas9 system, and NLRP3 deficiency was confirmed by RT-qPCR and western blotting. NLRP3 deficient SK-Hep1 cells showed delayed cell growth and decreased protein expression of PI3K, p-AKT, and pNF-κB when compared to NLRP3 complete SK-Hep1 cells. In addition, NLRP3 deficiency arrested the cell cycle at G1 phase through an increase in p21 and a reduction in CDK6. NLRP3 deficient SK-Hep1 cells also showed significantly delayed cell migration, invasion, and wound healing. The expression of epithelial-mesenchymal transition signaling molecules, such as N-cadherin and MMP-9, was found to be dramatically decreased in NLRP3 deficient SK-Hep1 cells compared to NLRP3 complete SK-Hep1 cells.

EGF Reverses Multi-drug Resistance via the p-ERK Pathway in HepG2/ADM and SMMC7721/ADM Hepatocellular Carcinoma Models

  • Yan, Feng;Bai, Li-Ping;Gao, Hua;Zhu, Chang-Ming;Lin, Li;Kang, Xiang-Peng
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권6호
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    • pp.2619-2623
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    • 2014
  • Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

Anti-tumor Efficacy of a Hepatocellular Carcinoma Vaccine Based on Dendritic Cells Combined with Tumor-derived Autophagosomes in Murine Models

  • Su, Shu;Zhou, Hao;Xue, Meng;Liu, Jing-Yu;Ding, Lei;Cao, Meng;Zhou, Zhen-Xian;Hu, Hong-Min;Wang, Li-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권5호
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    • pp.3109-3116
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    • 2013
  • The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

miR-101 Inhibiting Cell Proliferation, Migration and Invasion in Hepatocellular Carcinoma through Downregulating Girdin

  • Cao, Ke;Li, Jingjing;Zhao, Yong;Wang, Qi;Zeng, Qinghai;He, Siqi;Yu, Li;Zhou, Jianda;Cao, Peiguo
    • Molecules and Cells
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    • 제39권2호
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    • pp.96-102
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    • 2016
  • miR-101 is considered to play an important role in hepatocellular carcinoma (HCC), but the underlying molecular mechanism remains to be elucidated. Here, we aimed to confirm whether Girdin is a target gene of miR-101 and determine the tumor suppressor of miR-101 through Girdin pathway. In our previous studies, we firstly found Girdin protein was overexpressed in HCC tissues, and it closely correlated to tumor size, T stage, TNM stage and Edmondson-Steiner stage of HCC patients. After specific small interfering RNA of Girdin was transfected into HepG2 and Huh7.5.1 cells, the proliferation and invasion ability of tumor cells were significantly inhibited. In this study, we further explored the detailed molecular mechanism of Girdin in HCC. Interestingly, we found that miR-101 significantly low-expressed in HCC tissues compared with that in matched normal tissues while Girdin had a relative higher expression, and miR-101 was inversely correlated with Girdin expression. In addition, after miR-101 transfection, the proliferation, migration and invasion abilities of HepG2 cells were weakened. Furthermore, we confirmed that Girdin is a direct target gene of miR-101. Finally we confirmed Talen-mediated Girdin knockout markedly suppressed cell proliferation, migration and invasion in HCC while downregulation of miR-101 significantly restored the inhibitory effect. Our findings suggested that miR-101/Girdin axis could be a potential application of HCC treatment.

Synergistic antitumor activity of sorafenib and MG149 in hepatocellular carcinoma cells

  • Moon, Byul;Park, Mijin;Cho, Seung-Hyun;Kim, Kang Mo;Seo, Haeng Ran;Kim, Jeong-Hoon;Kim, Jung-Ae
    • BMB Reports
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    • 제55권10호
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    • pp.506-511
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    • 2022
  • Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress.

간세포암종의 세침흡인 세포학적 소견 - 247예에 대한 연구 - (Fine Needle Aspiration Cytology of Hepatocellular Carcinoma - A Study on 247 Cases -)

  • 이광길;이종태;최수임;박찬일
    • 대한세포병리학회지
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    • 제1권1호
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    • pp.1-17
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    • 1990
  • Hepatocellular carcinoma (HCC) is malignant tumor frequently occurring in Koreans. There have been few reports regarding the cytologic findings of fine needle aspiration (FNA) of HCC. Most have suggested a diagnostic problem in the cytology distinguishing HCC from some benign hepatic lesions-for example, a regeneration nodule in cirrhosis and liver cell adenoma. In spite of its high frequency in Korea, no cytologic study has been reported, concerning the FNA of HCC. In an attempt to achieve cytologic criteria for the diagnosis of HCC, the authors studied retrospectively cytopathologic findings of 247 cases of HCC. These cases were confirmed either by histoiogic examination including lobectomy, biopsy, or ceil block material, or, when tissue diagnosis was unavailable, by a high serum alpha-fetoprotein level (over 400 I. U.). All aspiration smears were stained by the Papanicolaou method. In each case, the smears were analyzed for cell patterns and various cytomorphology of the tumor cells. The smear background was assessed for the presence of tumor cell necrosis and inflammatory components and compared to that of metastatic carcinomas. The cell patterns were classified as trabecular, acinar, dispersed, and irregular. The cytologic parameters analyzed included the degree of nuclear atypia and the presence of mitoses, intranuclear cytoplasmic inclusions, nucleolar prominency, endothelial lining, multinucleated giant cells, eosinophiic globules, bile, and Mallory body. Most of the FNA of HCC showed markedly cellular smears. The tumor cells were most frequently arranged in a trabecular pattern (80.3%). The irregular (12.6%), the acinar (5.5%), and the dispersed patterns (1.7%) followed in decreasing frequency. Individual hepatoma cells were larger than normal liver cells. However, they had morphologic features characteristic of the hepatic cells the cells were round or polygonal, their cytoplasm was abundant and granular with eosinophilic or amphophilic stainability, and their nuclei were round to oval, located centrally, and tended to have prominent nucleoli. Anaplasia and pleomorphism of tumor cells were generally mild to moderate. These findings existed even in very well differentiated cases. Mitotic figures were present in about 85% of the cases. Prominent nucleoli were observed only in about half the cases. The frequency of other cytologic features was as follows intranuclear cytoplasmic inclusion in 86.8% : endothelial lining in 56.1% : bile in 19.8% : and giant cells in 60.1%. Clear cells were often present in 11.7%, Most aspiration smears of HCC displayed clean background without necrosis or inflammatory material in contrast to the dirty, necrotic background of metastatic cancers and cholangiocarcinomas. Based on the above mentioned features, it is suqqested that the cytologic critieria most important for the diagnosis of HCC include a markedly cellular smear, trabecular pattern, hepatocytoid appearance of tumor cells, endothelial lining, the presence of bile, giant cells, intranuclear cytoplasmic inclusions, and prominent nucleoli, Among these, trabecular pattern, endothelial lining, giant cells and clean smear background are points to be considered in differentiating HCC from metastatic and cholangiocellular carcinoma.

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