ArticleActa pharmacologica Sinica2011
Inhibition of hypoxia-inducible carbonic anhydrase-IX enhances hexokinase II inhibitor-induced hepatocellular carcinoma cell apoptosis.
Article in Acta pharmacologica Sinica, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism.Bioactive materials · 2025Article
- Identification and validation of icaritin-associated prognostic genes in hepatocellular carcinoma through network pharmacology, bioinformatics analysis, and cellular experiments.Frontiers in immunology · 2025Article
- NRF1-Induced lncRNA DDX11-AS1 Contributes to the Progression of Hepatocellular Carcinoma via Activating CA9 Expression and the MEK/ERK Pathway.Journal of hepatocellular carcinoma · 2025Article
- The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- Arenobufagin increases the sensitivity of gastric cancer to cisplatin via alkaliptosis.Heliyon · 2023Article
- Hypoxia-induced reprogramming of glucose-dependent metabolic pathways maintains the stemness of human bone marrow-derived endothelial progenitor cells.Scientific reports · 2023Article
- CA10 is associated with HBV-related hepatocarcinogenesis.Biochemistry and biophysics reports · 2022Article
- A novel hypoxia gene signature indicates prognosis and immune microenvironments characters in patients with hepatocellular carcinoma.Journal of cellular and molecular medicine · 2021Article
- Carbonic anhydrase-IX inhibition enhances the efficacy of hexokinase II inhibitor for hepatocellular carcinoma in a murine model.Journal of bioenergetics and biomembranes · 2019Article
- The embryonic transcription factor Brachyury confers chordoma chemoresistance via upregulating CA9.American journal of translational research · 2018Article
- Review
- Hexokinase 2 (HK2), the tumor promoter in glioma, is downregulated by miR-218/Bmi1 pathway.PloS one · 2017Article
- The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside.Journal of bioenergetics and biomembranes · 2016Review
- Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma.Virchows Archiv : an international journal of pathology · 2015Article
- Expression of carbonic anhydrase 9 is a novel prognostic marker in resectable hepatocellular carcinoma.Virchows Archiv : an international journal of pathology · 2015Article
- Targeting carbonic anhydrase IX activity and expression.Molecules (Basel, Switzerland) · 2015Review
- Advances in Anti-Cancer Drug Development Targeting Carbonic Anhydrase IX and XII.Topics in anti-cancer research · 2015Article
- Expression of hypoxic marker carbonic anhydrase IX predicts poor prognosis in resectable hepatocellular carcinoma.PloS one · 2015Article
- The potential of liposomes with carbonic anhydrase IX to deliver anticancer ingredients to cancer cells in vivo.International journal of molecular sciences · 2014Review
- Molecular probes for imaging of hypoxia in the retina.Bioconjugate chemistry · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe hypoxic condition within large or infiltrative hypovascular tumors produces intracellular acidification, which could activate many signaling pathways and augment cancer cell growth and invasion. Carbonic anhydrase-IX (CA-IX) is an enzyme lowering pH. This study is to examine whether hypoxia induces CA-IX in hepatocellular carcinoma (HCC) cells, and to evaluate its clinical implication in HCC patients.
methodsHuman HCC cell lines (Huh-7 and HepG2 cells) were used, and cell growth was assessed using MTS assay. CA-IX expression and apoptotic/kinase signaling were evaluated using immunoblotting. The cells were transfected with CA-IX-specific siRNA, or treated with its inhibitor 4-(2-aminoethyl) benzenesulfonamide (CAI#1), and/or the hexokinase II inhibitor, 3-bromopyruvate (3-BP). A clinic pathological analysis of 69 patients who underwent an HCC resection was performed using a tissue array.
resultsIncubation of HCC cells under hypoxia (1% O₂, 5% CO₂, 94% N₂) for 36 h significantly increased CA-IX expression level. CAI#1 (400 μmol/L) or CA-IX siRNA (100 μmol/L) did not influence HCC cell growth and induce apoptosis. However, CAI#1 or CA-IX siRNA at these concentrations enhanced the apoptosis induced by 3-BP (100 μmol/L). This enhancement was attributed to increased ER stress and JNK activation, as compared with 3-BP alone. Furthermore, a clinic pathological analysis of 69 HCC patients revealed that tumor CA-IX intensity was inversely related to E-cadherin intensity.
conclusionInhibition of hypoxia-induced CA-IX enhances hexokinase II inhibitor-induced HCC apoptosis. Furthermore, CA-IX expression profiles may have prognostic implications in HCC patients. Thus, the inhibition of CA-IX, in combination with a hexokinase II inhibitor, may be therapeutically useful in patients with HCCs that are aggressively growing in a hypoxic environment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.