Abstract:
:Triple-negative breast cancer (TNBC), which is estrogen receptor (ER)-negative, progesterone receptor‑negative and is also negative for HER2 expression, remains a great clinical challenge due to its strong resistance to chemotherapy at the late stage of treatment and relatively unfavorable prognosis. Gemcitabine has been approved by the FDA/SFDA for use as a first-line therapeutic drug against advanced or metastatic breast cancer. Therefore, the clarification of the mechanisms underlying gemcitabine-acquired resistance is of particular importance for the optimal management of TNBC. A number of studies have revealed that autophagy, which has been found to protect cancer cells from anti-cancer drug-induced death, may contribute to the development of drug resistance. However, the association between autophagy and gemcitabine treatment in TNBC cells has yet to be defined. Our study clearly demonstrates that gemcitabine is able to induce mTOR-independent autophagy in human triple‑negative MDA-MB-231 breast cancer cells. In addition, we demonstrate that autophagy protects MDA-MB-231 cells from gemcitabine-induced cell growth inhibition and apoptosis, indicating that gemcitabine can activate autophagy to impair the sensitivity of MDA-MB‑231 cells. Furthermore, as shown by our results, the inhibition of gemcitabine-induced autophagy by chloroquine shifts the expression of the p53 protein, Bcl-2 family proteins and the relative Bax/Bcl-xL ratio in favor of promoting apoptosis. These results reveal that the inhibition of apoptosis may be one of the mechanisms of autophagy-induced cytoprotection in gemcitabine-treated MDA-MB-231 cells. The apoptotic and autophagic processes constitute a mutual inhibition system and jointly seal the fate of TNBC cells that are exposed to gemcitabine. Thus, our study suggests that the combination of an autophagic inhibitor and gemcitabine as a therapeutic strategy may represent a promising approach with greater clinical efficacy for patients with TNBC. However, extended preclinical trials are required to further determine the positive effects of the inhibition of autophagy on the efficacy of gemcitabine.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Chen M,He M,Song Y,Chen L,Xiao P,Wan X,Dai F,Shen Pdoi
10.3892/ijmm.2014.1772subject
Has Abstractpub_date
2014-07-01 00:00:00pages
276-82issue
1eissn
1107-3756issn
1791-244Xjournal_volume
34pub_type
杂志文章abstract::The basic helix loop helix (bHLH) transcription factor DEC2 is associated with the regulation of apoptosis, circadian rhythm and the response to hypoxia. However, the significance of DEC2 in pancreatic cancer remains unknown. Here, we showed for the first time that DEC2 inhibits the...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2012.1037
更新日期:2012-09-01 00:00:00
abstract::The molecular mechanisms underlying entry of group B Streptococci (GBS) into human endothelial cells are not yet fully understood. This study is centered on the triggering of signaling cascade in human umbilical vein endothelial cells (HUVEC) during their interaction with different GBS serotypes/strains (type III: 803...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2005-05-01 00:00:00
abstract::Rac1, an intracellular signal transducer, regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac1 has been reported in several human cancers. However, the underlying mechanisms are not well understood. In the present study, we evaluate...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2011.775
更新日期:2011-11-01 00:00:00
abstract::Insulinoma-associated protein 2 (IA-2) is the major autoantigen that contributes to the pathogenesis of type 1 diabetes (T1D). IA-2-deficient (IA-2-/-) mice showed impaired insulin secretion after intraperitoneal injection of glucose as well as elevated glucose level in a glucose tolerance test. Despite the fact that ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm_00000201
更新日期:2009-07-01 00:00:00
abstract::The present study aimed to explore possible prognostic marker genes in glioblastoma (GBM). Differentially expressed genes (DEGs) were screened by comparing microarray data of tumor and normal tissue samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset GSE22866. Subsequently, the pr...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3422
更新日期:2018-04-01 00:00:00
abstract::The active fraction of the extract of Asiasari radix, the 60% methanol chromatographic fraction from the ethyl acetate layer (PPAR), was used to investigate the melanogenesis signal pathway in B16F10 melanoma cells. PPAR led to significantly decreased melanin synthesis and tyrosinase activity in a dose-dependent manne...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2010-02-01 00:00:00
abstract::Elucidation of the molecular mechanisms governing the osteogenic differentiation of human mesenchymal stem cells (hMSCs) is of great importance for improving the treatment of bone-related diseases. MicroRNAs (miRNAs or miRs), a class of small non-coding RNAs, are critical in a number of biological processes, including...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2275
更新日期:2015-09-01 00:00:00
abstract::The parathormone (PTH) production is controlled by calcium and vitamin D, which interact with the calcium-sensing receptor (CaSR) and vitamin D receptor (VDR), respectively. All of these elements control calcium homeostasis, which is crucial for many physiological processes. Thus, impairment of the upstream component ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2006-05-01 00:00:00
abstract::Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. Transforming growth factor-β1 (TGF-β1) signaling has been considered as a trigger causally contributing to pathological cardiac hypertrophy. Asiatic acid (AA) is a triterpenoid compound extracted from Centella asiatica and exhibits a variety of...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.1781
更新日期:2014-08-01 00:00:00
abstract::The aim of this study was to identify key genes associated with coronary artery disease (CAD) and to explore the related signaling pathways. Gene expression profiles of 110 CAD and 112 non-CAD, healthy patients [CAD index (CADi) >23 and =0, respectively] were downloaded from the Gene Expression Omnibus (GEO) database ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.1817
更新日期:2014-09-01 00:00:00
abstract::Microglia of the central nervous system serve a variety of functions that may ultimately lead to the development or detriment of neighboring neuronal and vascular cells. These scavengers of the nervous system have been associated with a variety of neurodegenerative disorders, but the toxic potential of microglia is eq...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2007-02-01 00:00:00
abstract::Apoptosis induced by docetaxel that interferes with microtubule polymerization dynamics and is used clinically to treat advanced cancers, has not been fully defined in squamous cell carcinoma. In this study, apoptotic events involved in docetaxel treatment were investigated. When the human oral squamous cell carcinoma...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2005-04-01 00:00:00
abstract::To gain a better understanding of the mechanisms that underpin aortic calcification, rodent models have been previously utilised. Regions of calcium and phosphate deposition are commonly visualised using labor-intensive two-dimensional histomorphometric techniques. In this study, we developed a novel micro-computed to...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1490
更新日期:2013-11-01 00:00:00
abstract::Apelin, the endogenous ligand of APJ which is a member of G protein-coupled receptors, has been shown to be expressed in a variety of tissues in vivo and to exert significant biological effects. Studies have indicated that the apelin/APJ system is involved in the regulation of a variety of physiological functions and ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:10.3892/ijmm.2016.2544
更新日期:2016-05-01 00:00:00
abstract::Serum response factor (SRF) is a transcription factor that has important roles in tumor progression. However, its role in cervical cancer cell proliferation and invasion remains unclear. The present study revealed that SRF silencing constrained cervical cancer cell proliferation and invasion via controlling early grow...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3954
更新日期:2019-01-01 00:00:00
abstract::The ectromelia virus (ECTV) is a mouse specific Orthopoxvirus that causes lethal infection in some mouse strains. ECTV infection of these mouse strains has been used as a valuable model for understanding the interplay between Orthopoxvirus species and their hosts, including variola virus in humans. Although poxviruses...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3655
更新日期:2018-08-01 00:00:00
abstract::Damage to the bronchial epithelium leads to persistent inflammation and airway remodelling in various respiratory diseases, such as asthma and chronic obstructive pulmonary disease. To date, the mechanisms underlying bronchial epithelial cell damage and death by common allergens remain largely unknown. The aim of the ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3310
更新日期:2018-02-01 00:00:00
abstract::Aberrant glycosylation is a universal feature of cancer cells. There are quantitative and qualitative changes in expression of gangliosides observed in tumors of a neuroectodermal origin such as neuroblastoma, melanoma and astrocytoma. The presence of large amounts of GD2 ganglioside on neuroblastoma cells, as compare...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2007-05-01 00:00:00
abstract::Van der Woude syndrome (VWS) is the most common autosomal dominant disorder with characteristic lip pits and clefts of the lip and/or palate (CL/P). The interferon regulatory factor 6 gene (IRF6) has been recently identified as the gene mutated in patients with VWS. Here, we report two novel mutations of IRF6 in two u...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::The pathologic mechanisms of pulmonary fibrosis (PF), one of the most common chronic pulmonary diseases, remain unclear. Napsin A is an aspartic proteinase that has been regarded as a hallmark of pulmonary adenocarcinoma. The present study aimed to investigate the specific function and molecular mechanisms of Napsin A ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2020.4565
更新日期:2020-07-01 00:00:00
abstract::Inflammation in the brain, characterized by the activation of microglia, is believed to participate in the pathogenesis of Parkinson's disease. Biochanin A, an O-methylated isoflavone, is a natural organic compound and is classified as a phytoestrogen. In this study, using murine BV2 microglial cells, we investigated ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.2020
更新日期:2015-02-01 00:00:00
abstract::Apoptosis plays a critical role in the pathogenesis of chronic myocardial ischemia (CMI) and heart failure (HF). Endoplasmic reticulum stress (ERS) is one of the newly defined signaling pathways which initiate apoptosis. Previous studies have shown that ERS-associated apoptosis is involved in the pathogenesis of HF in...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2011.612
更新日期:2011-04-01 00:00:00
abstract::Evidence is available that exendin-4 (EX4), a glucagon-like peptide-1 receptor (GLP-1R) agonist acutely stimulates hypothalamo-pituitary-adrenal (HPA) axis in the rat. EX4 is a potent insulinotropic agent, which is currently under clinical trial for treatment of type 2 diabetes. Since diabetes is known to affect adren...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::Orientia tsutsugamushi (O. tsutsugamushi), the causative agent of scrub typhus, is an obligate intracellular pathogen. Recent studies have demonstrated the complete genome of O. tsutsugamushi. However, the route and detailed molecular mechanism for O. tsutsugamushi to get accessed into mammalian cells remains unclear....
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2012.967
更新日期:2012-07-01 00:00:00
abstract::Mechanical stress and genetic factors play important roles in the occurrence of thoracic ossification of ligament flavum (TOLF), which can occur at one, two, or multiple levels of the spine. It is unclear whether single- and multiple-level TOLF differ in terms of osteogenic differentiation potency and osteogenesis-rel...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2803
更新日期:2017-01-01 00:00:00
abstract::ARHGAP1, ARHGAP2, ARHGAP3, ARHGAP4, ARHGAP5, ARHGAP6, ARHGAP7 (DLC1), ARHGAP8, ARHGAP9, ARHGAP10, ARHGAP12, ARHGAP13 (SRGAP1), ARHGAP14 (SRGAP2), ARHGAP15, ARHGAP17 (RICH1), ARHGAP18, ARHGAP19, ARHGAP20, ARHGAP21, ARHGAP22, ARHGAP23, ARHGAP24, ARHGAP25, ARHGAP26, STARD13 (DLC2), HA-1, GMIP, PARG1, RACGAP1, PIK3R1, PIK...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2004-11-01 00:00:00
abstract::Paeonol (2'-hydroxy-4'-methoxyacetophenone) is an active component isolated from the root of Paeonia Suffruticosa Andrews. We previously found that paeonol inhibited vascular cell adhesion molecule-1 (VCAM‑1) expression, and thus may be useful for the prevention and treatment of rabbit atherosclerosis (AS); however, t...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2778
更新日期:2016-12-01 00:00:00
abstract::microRNAs (miRNAs) are important both in early cardiogenesis and in the process of heart maturation. The aim of this study was to determine the stage-specific expression of miRNAs in human fetal heart in order to identify valuable targets for further study of heart defects. Affymetrix microarrays were used to obtain m...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.1691
更新日期:2014-05-01 00:00:00
abstract::The differentiation of atrial fibroblasts into myofibroblasts is a critical event in atrial fibrosis. One of the most important factors in atrial fibroblast differentiation is transforming growth factor-β1 (TGF-β1). Accumulating evidence indicates that sodium tanshinone IIA sulfonate (STS) possesses antifibrotic prope...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2015.2087
更新日期:2015-04-01 00:00:00
abstract::As hyperprolactinemia is observed in patients with bromocriptine‑resistant prolactinoma, prolactin (PRL) has been implicated in the development of bromocriptine resistance. Since PRL primarily mediates cell survival and drug resistance via the Janus kinase‑2 (JAK2)/signal transducer and activator of transcription 5A (...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2020.4784
更新日期:2021-01-01 00:00:00