Abstract:
:This study aims to explore the effect and mechanism of pyruvate kinase M2 (PKM2) on chemotherapy resistance of estrogen receptor-positive breast cancer (ER BC) by regulating aerobic glycolysis. The expression of PKM2 in ER BC MCF-7 cells, T47D cells and MCF-7/ADR cells (which are subject to adriamycin/ADR induction) were determined by quantitative real-time PCR and western blot. MCF-7/ADR (M/A) cells were grouped into blank group (M/A), negative group (M/A+NC), low expression of PKM2 group (M/A+si-PKM2 group), overexpression of PKM2 group (M/A+PKM2 group) and glycolysis inhibition group (M/A+PKM2+2-DG group). Quantitative real-time PCR and western blot were applied to measure the expressions of PKM2, multidrug resistance, and glutathione-S-transferase π. Glucose and lactic acid kit was used to detect the amount of glucose uptake and lactic production. Cell variability, clone formation ability, and cell apoptosis were respectively measured by MTT, clone formation assay, and flow cytometry. Transwell assay and scratch assay were applied for cell invasion and migration ability. By overexpressing PKM2 in MCF-7 and T47D cells and using 2-DG, the effect on sensitivity of adriamycin amycin was explored. MCF-7/ADR cells have both elevated mRNA and protein expressions of PKM2 when compared with MCF-7 cells (both P<0.05). The cell activity of the M/A+si-PKM2+ADR group was notably lower than that in the M/A+ADR group and M/A+NC+ADR group (both P<0.05). In the M/A+si-PKM2 group, expressions of PKM2, multidrug resistance, and glutathione-S-transferase π, along with the amount of glucose uptake and lactic production, as well as cell variability, clone formation ability, and cell invasion and migration ability were inhibited, whereas cell apoptosis was increased in comparison with the M/A group and M/A+NC group (all P<0.05). On comparing with both the M/A group and the M/A+NC group, the M/A+si-PKM2 group displayed contrary tendency with the M/A+PKM2 group. The M/A+PKM2+2-DG group had elevated PKM2 expression compared with the M/A group and the M/A+NC group (all P<0.05). In MCF-7 and T47D cells with overexpression of PKM2, the sensitivity to adriamycin amycin, and cell apoptosis were suppressed, whereas the clone formation, invasion, and migration ability were enhanced. After 2-DG, the sensitivity on MCF-7 and T47D cells was enhanced while clone formation, invasion, migration and cell apoptosis rate were decreased (all P<0.05). PKM2 enhances chemotherapy resistance on ER BC by promoting aerobic glycolysis.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Qian Y,Bi L,Yang Y,Wang Ddoi
10.1097/CAD.0000000000000624subject
Has Abstractpub_date
2018-08-01 00:00:00pages
616-627issue
7eissn
0959-4973issn
1473-5741journal_volume
29pub_type
杂志文章abstract::The aim of this review is to summarize currently available information on the rapid screening and initial characterization of the different mechanisms of resistance to hydrophilic [e.g. methotrexate (MTX)] and lipophilic antifolates [e.g. trimetrexate (TMTX)] in cultured mammalian cells using fluorescein-methotrexate ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199310000-00002
更新日期:1993-10-01 00:00:00
abstract::Glassy cell carcinoma (GCC) of the uterine cervix is a highly malignant tumor and has a poor prognosis. As yet, no effective systemic chemotherapy to this tumor has been reported. Here we describe a case of recurrent GCC that responded to paclitaxel and carboplatin combination treatment. The patient, a 32-year-old wom...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200108000-00010
更新日期:2001-08-01 00:00:00
abstract::Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this pr...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000473
更新日期:2017-04-01 00:00:00
abstract::RNA interference, a posttranscriptional gene-silencing mechanism, has received considerable attention for its potential as a new therapeutic strategy to treat human diseases and conditions including cancer. Various studies have supported a role for the R2 subunit of ribonucleotide reductase in cancer progression and m...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328013c04f
更新日期:2007-04-01 00:00:00
abstract::Cantharidin is a natural toxin that possesses potent anti-tumor properties. Its clinical application, however, is limited due to severe side-effects. Its cytotoxicity is believed to be mediated by the inhibition of serine/threonine protein phosphatase 2A. In order to identify new compounds with potential clinical ther...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000217428.90325.35
更新日期:2006-09-01 00:00:00
abstract::In this study, we investigated the molecular mechanism of doxorubicin (dxr)-induced cytotoxicity on Jurkat cells - a model cell of human acute lymphoblastic leukemia - under normoxic (20% O2) and hypoxic (5% O2) conditions. Using in-cell western analysis, immunofluorescence, flow cytometry analysis, and biochemical in...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000223
更新日期:2015-07-01 00:00:00
abstract::Urothelial carcinoma of the bladder accounts for over 95% of bladder tumours in France. The incidence of this disease is increasing in industrialised countries. Several types of bladder cancer can be distinguished: (1) superficial tumours which have a risk of recurrence and progression, although conservative treatment...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:
更新日期:2000-10-01 00:00:00
abstract::Lung cancer is considered the number one killer among all cancers. Recent observations have altered the treatment paradigm for non-small-cell lung cancer (NSCLC). The discovery of activating mutations in the epidermal growth factor receptor and anaplastic lymphoma kinase positivity has made personalized treatment for ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0b013e3283585149
更新日期:2012-11-01 00:00:00
abstract::Cyclosporin A (CsA) is a calcium antagonist and can enhance the efficacy of some protein drugs, but its mechanism remains unknown. In this study, MAP30, a ribosome-inactivating protein reported to have apoptotic effects on cancer cells, was fused with S3, an epidermal growth factor receptor (EGFR)-targeting peptide. I...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000649
更新日期:2018-09-01 00:00:00
abstract::Esophageal cancer is one of the fatal cancers around the world. Dexmedetomidine (DEX) is widely used during anesthesia of esophageal cancer surgery. Nevertheless, the role of DEX in the progression of esophageal cancer remains barely known. The proliferation, apoptosis and metastasis of esophageal cancer cells were de...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000934
更新日期:2020-08-01 00:00:00
abstract::We investigated whether Ukrain modulates the malignant phenotype of clear cell renal cell carcinoma (ccRCC) cells Caki-1, Caki-2, and ACHN treated with four doses (5, 10, 20, and 40 μmol/l) for 24 and 48 h. The epithelial-to-mesenchymal transition markers E-cadherin, β-catenin, and vimentin were analyzed by immunofluo...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328346c7f7
更新日期:2011-09-01 00:00:00
abstract::The delivery formulation 5-FU-MS [5-fluorouracil (5-FU) incorporated in microspheres composed of a poly(glycolide-co-lactide) matrix] slowly releases 5-FU over 3 weeks. 5-FU-MS delivers higher concentrations of the drug to the i.p. tissues for a longer period of time with lower blood plasma concentrations than does an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199803000-00012
更新日期:1998-03-01 00:00:00
abstract::The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000342
更新日期:2016-06-01 00:00:00
abstract::Ecteinascidin 743 (Et743) is an interesting compound in phase II/III clinical trials. Its chemistry is complex, its mechanism of action is original and it is active in human cancers, such as sarcomas refractory to conventional chemotherapy. The present review describes the discovery of the drug, its specific interacti...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-200207000-00001
更新日期:2002-07-01 00:00:00
abstract::Para-toluenesulfonamide (PTS), active ingredient being PTS, is a new anticancer drug applied through local intratumoral injection. The aim of this phase II clinical trial was to investigate the response and toxicity of standard gemcitabine (GEM) plus cisplatin (CIS) chemotherapy with concurrent intratumoral injection ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32832fe48f
更新日期:2009-10-01 00:00:00
abstract::A lack of cross-resistance between the aromatase inhibitors (AIs) provides evidence to suggest that there are clinical differences between these agents. Available data from clinical trials indicate that patients exposed to nonsteroidal AIs may benefit from a steroidal compound of similar biochemical potency, and durab...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/01.cad.0000277875.81122.25
更新日期:2008-03-01 00:00:00
abstract::The aim of this study was to evaluate the anticancer and antitumor activities of ceramide analog 315 in nude mice. Nude mice (n=10) were injected bilaterally with 5×10 MDA-MB-231 cells on each side. Tumors were allowed to form for 2 weeks. The mice were then divided into two groups (n=5 in each group). The control gro...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000675
更新日期:2018-10-01 00:00:00
abstract::Derivatives of bis-aryl urea have been widely investigated for their various biological activities, such as antiviral, anti-inflammatory and antiproliferative. We evaluated a new chemical entity consisting of bis-aryl urea moiety, N69B, for its anticancer activities and explored their underlying molecular mechanism. T...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000898
更新日期:2020-06-01 00:00:00
abstract::Twelve patients received intrapleural instilments of the cytostatic agent mitoxantrone in a total dosage of 30 mg for locoregional palliative therapy of malignant pleural effusion. Effusion could be stopped for a mean period of 3.2 months in 11 patients. ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199202000-00003
更新日期:1992-02-01 00:00:00
abstract::Pancreatic neuroendocrine tumors (PNETs) are rare malignancies that arise from the islets of Langerhans. The role of standard chemotherapy in advanced well-differentiated PNETs remains to be defined. Sunitinib is an oral multitargeted inhibitor with antiangiogenic and antitumor properties that has shown significant im...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e328344484b
更新日期:2011-06-01 00:00:00
abstract::Lipoplatin, currently under phase III evaluation, is a novel liposomal cisplatin formulation highly effective against cancers. Lipoplatin has eliminated or reduced the systemic toxicity frequently seen for cisplatin. The objective of the present study was to determine whether the cytotoxic effect of lipoplatin is depe...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200603000-00010
更新日期:2006-03-01 00:00:00
abstract::Taxol is an antitumor drug which, as its mechanism of action, promotes microtubule assembly in vitro. Camptothecin (CPT) is an anticancer agent with the peculiar mechanism of poisoning eukaryotic DNA topoisomerase I. Both drugs are in clinical trials and their chemotherapeutic efficacy seems promising in refractory hu...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199607000-00007
更新日期:1996-07-01 00:00:00
abstract::Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Its effect on pancreatic cancer is, however, unknown and the mechanism is unclear. The study aims to investigate its antitumor activity and underlying mechanisms in human pancreatic cance...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283212ade
更新日期:2009-02-01 00:00:00
abstract::A phase II study was performed to assess the safety and efficacy of mitoxantrone and cisplatin in locally recurrent and/or metastatic carcinomas of the salivary glands. Between May 1997 and March 2001, a total of 14 patients were entered on this trial. All of them had previously undergone radical resection and 10 were...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200206000-00007
更新日期:2002-06-01 00:00:00
abstract::E7070 is a novel sulfonamide anticancer agent that arrests the G(1)/S phase of the cell cycle. Preclinical and phase I studies have demonstrated non-linear pharmacokinetics (PK) of the drug. A population PK analysis revealed that the human plasma concentration-time data were best described by a three-compartment model...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200307000-00003
更新日期:2003-07-01 00:00:00
abstract::In this study, we tried to define in vitro interactions of two antitumor agents that have different sites and different mechanisms of action. Vinblastine (VLB) in combination with human recombinant interferon-alpha A/D (rHuIFN-alpha A/D) and in combination with murine recombinant interferon-gamma (rMuIFN-gamma) was st...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199402000-00008
更新日期:1994-02-01 00:00:00
abstract::The camptothecin derivative 9-nitrocamptothecin (9-NC) has demonstrated clinical activity in patients with ovarian and pancreatic carcinomas. Preclinical studies have shown promising activity of 9-NC for melanoma. We have thus conducted a phase II clinical trial of 9-NC for patients with metastatic cutaneous and uveal...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200202000-00009
更新日期:2002-02-01 00:00:00
abstract::Overexpression of the multidrug resistance MDR1 gene product P-glycoprotein and/or the multidrug resistance-associated protein MRP confers multidrug resistance to cancer cells. The pipecolinate derivative VX-710 has previously been demonstrated to reverse MDR1-mediated multidrug resistance at concentrations of 0.5-2.5...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199702000-00005
更新日期:1997-02-01 00:00:00
abstract::Preoperative chemoradiotherapy (CRT) is generally performed for locally advanced rectal cancer (LARC, cStage 2 or 3) to improve local disease control and patient survival. The pathological tumor response to CRT is a surrogate marker that is associated with oncological outcome. Thus, markers that predict the response t...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000391
更新日期:2016-09-01 00:00:00
abstract::We chose to treat malignant pleural mesothelioma with a combination of docetaxel and irinotecan (CPT-11), because there have been preliminary reports that CPT-11 is active against mesothelioma, and docetaxel and CPT-11 were the most active agents in our in vitro experiments in human mesothelioma cell lines. Fifteen pr...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-200004000-00005
更新日期:2000-04-01 00:00:00