Abstract:
:Gemcitabine is the cornerstone of pancreatic cancer treatment. Although effective in most patients, development of tumor resistance to gemcitabine can critically limit its efficacy. The mechanisms responsible for this phenomenon remain elusive, but evidence suggests that ubiquitin-specific peptidases (USPs) may be key regulators in cancer chemo-resistance. The present study aimed to investigate the role of USP9X in gemcitabine resistance using in vitro pancreatic cell lines and a mouse xenograft model. We found that the expression of USP9X in pancreatic cancer cells was positively correlated with gemcitabine resistance, and that inhibition of USP9X by WP1130 sensitized pancreatic cancer cells to gemcitabine. Gemcitabine induced autophagy, and blocking autophagy with chloroquine improved sensitivity to gemcitabine. We also found that WP1130 inhibited gemcitabine-induced autophagy, and blocking autophagy abolished the sensitization effect of WP1130 on gemcitabine in pancreatic cancer cells. Finally, combined gemcitabine and WP1130 treatment enhanced the anti-tumor effect of gemcitabine by suppressing autophagy in vivo. Taken together, these results demonstrate that inhibition of USP9X sensitized pancreatic cancer cells to gemcitabine by inhibiting autophagy, which provides a novel insight into gemcitabine resistance in pancreatic cancer.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Ma T,Chen W,Zhi X,Liu H,Zhou Y,Chen BW,Hu L,Shen J,Zheng X,Zhang S,Zhang B,Li H,Liang Tdoi
10.1016/j.canlet.2018.08.010subject
Has Abstractpub_date
2018-11-01 00:00:00pages
129-138eissn
0304-3835issn
1872-7980pii
S0304-3835(18)30522-6journal_volume
436pub_type
杂志文章相关文献
CANCER LETTERS文献大全abstract::Mammaglobin B is a recently-isolated gene speculated to belong to the uteroglobin gene family and is overexpressed in primary breast cancers. We investigated mammaglobin B mRNA expression in various cancers of the digestive system. Given the absence of mammaglobin B expression in normal lymph nodes, we also assessed t...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(99)00378-x
更新日期:2000-03-13 00:00:00
abstract::Primary cultures of mouse embryo cells are more efficient in excising DNA-carcinogen adducts resulting from exposure to either 7-bromomethylbenz-[alpha]anthracene or the more carcinogen 7-bromomethyl-12-methylbenz[alpha]anthracene than are mouse L 929 cell suspension cultures. However, within each of these systems, th...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(79)80103-2
更新日期:1979-07-01 00:00:00
abstract::As the frequent emergency of resistant tumor cells during treatment, the development of new agents with new modes of action attracts a great deal of interest. Polybia-MPI was a short cationic alpha-helical amphiphilic peptide that has selective toxicity toward cancer cells but no hemolytic activity. Its target selecti...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2008.12.027
更新日期:2009-06-08 00:00:00
abstract::Microphthalmia-associated transcription factor (MITF) is expressed in melanomas and has a critical role in melanocyte development and transformation. Because inhibition of MITF inhibits cell growth in melanoma, MITF is a potential therapeutic target molecule. Here, we report the identification of CH6868398, which has ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2017.09.008
更新日期:2017-11-28 00:00:00
abstract::Atg4 proteases are cysteine proteases, which are well known for their crucial roles in the lipidation and delipidation of LC3 during the autophagy process. At least four human Atg4 homologs have been reported according to their sequence homology to the yeast Saccharomyces cerevisiae (Sc) Atg4. Accumulating evidence ha...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2016.01.022
更新日期:2016-04-01 00:00:00
abstract::The study describes the kinetics of demethylation of mononitrosocaffeidine (MNC), a new asymmetric N-nitrosamine derived from caffeine. The demethylation of its precursor compound caffeidine was also studied. The results presented here suggest (a) that liver microsomes from fasted rats preferentially demethylate the N...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(94)90071-x
更新日期:1994-04-29 00:00:00
abstract::We subcutaneously inoculated parental and glioma cells genetically engineered to express interleukin-2 (SR/IL-2) into syngeneic mice. The tumor growth of the transfectants was slower than that of the parental cells. We then stereotactically inoculated transfectants into the brains of mice. The survival of the mice inj...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(98)00268-7
更新日期:1999-01-08 00:00:00
abstract::The expression of DNA-topoisomerase II was analysed at the protein level in newly diagnosed cases of acute lymphoblastic leukemia (ALL) in children. Blast cells obtained from 81 children with untreated ALL were determined by means of immunocytochemistry. Of the ALL, 49 (60%) were positive for topoisomerase II and 32 (...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(94)90368-9
更新日期:1994-09-15 00:00:00
abstract::The Chinese Glioma Cooperative Group (CGCG) Guideline Panel for adult diffuse gliomas provided recommendations for diagnostic and therapeutic procedures. The Panel covered all fields of expertise in neuro-oncology, i.e. neurosurgeons, neurologists, neuropathologists, neuroradiologists, radiation and medical oncologist...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2016.01.024
更新日期:2016-06-01 00:00:00
abstract::Lumican is a small leucine-rich proteoglycan (SLRP) of the extracellular matrix (ECM) with anti-tumor activity. We recently demonstrated that lumican inhibits the migration of melanoma cells and identified beta1 integrin as mediator of this effect [M.F. D'Onofrio, S. Brézillon, T. Baranek, C. Perreau, P.J. Roughley, F...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2009.03.032
更新日期:2009-09-28 00:00:00
abstract::Membrane-type 1 matrix metalloproteinase (MT1-MMP), which hydrolyzes type I collagen and activates MMP-2, are deeply involved in angiogenesis as well as in tumor cell invasion and metastasis. We previously screened a number of natural and synthetic compounds to obtain a specific inhibitor of MT1-MMP and observed that ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2004.03.008
更新日期:2004-07-08 00:00:00
abstract::YM529, a new third generation bisphosphonate, induced apoptosis of a human breast cancer cell line, MX-1. Cytotoxic activity of YM529 was more potent than that of incadronate. YM529 activated caspase-9, but not caspase-8, and induced the release of cytochrome c into cytosol. YM529 increased Bax expression and decrease...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2007.01.008
更新日期:2007-08-08 00:00:00
abstract::To determine Toxoplasma gondii antibodies in cancer patients, 267 cancer patients were studied using ELISA and higher positivity rates of T. gondii IgG were detected than the control. The positivity rates of T. gondii IgG in nasopharyngeal carcinoma, rectal cancer groups were significantly higher than the other cancer...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2007.02.011
更新日期:2007-08-28 00:00:00
abstract::Far-infrared (FIR) radiation is known to lessen the risk of angiogenesis-related diseases including cancer. Because deficiency of secretory clusterin (sCLU) has been reported to inhibit angiogenesis of endothelial cells (EC), we investigated using human umbilical vein EC (HUVEC) whether sCLU mediates the inhibitory ef...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2013.12.011
更新日期:2014-04-28 00:00:00
abstract::Chronic myeloproliferative disorders (CMPD) are clonal disorders of the hematopoietic stem cell. The myeloid lineage shows increased proliferation with effective maturation, while peripheral leukocytosis, thrombocytosis or elevated red blood cell mass are found. In Philadelphia negative CMPD recurrent cytogenetic abno...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2007.02.009
更新日期:2007-09-18 00:00:00
abstract::The effect of pretreatment of skin of Sencar mice with topically applied tannic acid, quercetin and green tea polyphenols (GTP) on the skin tumor initiating activity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-2) has been evaluated. The animals were pretreated with ...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(88)90232-7
更新日期:1988-09-01 00:00:00
abstract::Development of chemotherapy resistance remains a major obstacle for glioma management. Exosome-mediated transfer of circular RNAs (circRNAs) are being found to have relevance to many human cancers, including glioma. The purpose of this study is to explore the effect and underlying mechanism of exosomal circRNA nuclear...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2020.03.002
更新日期:2020-06-01 00:00:00
abstract::To examine the role of diabetes in pancreatic cancer, 4 groups of Chinese hamsters--2 from genetically diabetic and 2 from non-diabetic lines--were treated with N-nitrosobis(2-oxo-propyl)amine (BOP) at different dose levels and intervals. In one group (referred to as the VA group), BOP was given weekly at a 5 mg/kg bo...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(87)90014-0
更新日期:1987-02-01 00:00:00
abstract::Deregulation of cell metabolism is an established cancer hallmark that contributes to tumor initiation and progression, as well as tumor heterogeneity. In solid tumors, alterations in different metabolic pathways, including glycolysis, pentose phosphate pathway, glutaminolysis and fatty acid metabolism, support the hi...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2020.02.034
更新日期:2020-05-01 00:00:00
abstract::Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 pat...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2018.04.020
更新日期:2018-08-01 00:00:00
abstract::Costunolide (CT), a sesquiterpene lactone constituent isolated from Saussurea lappa (Compositae), exerted an antiangiogenic effect. CT selectively inhibited the endothelial cell proliferation induced by vascular endothelial growth factor (VEGF). Further, CT was also found to inhibit the VEGF-induced chemotaxis of huma...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(02)00361-0
更新日期:2002-12-10 00:00:00
abstract::MICAL2 is a tumor-promoting factor involved in cell migration, invasion, deformation, and proliferation not yet fully explored in lung adenocarcinoma (LUAD). This study demonstrated that MICAL2 was overexpressed and cytoplasm-enriched in LUAD tissues. Moreover, high cytoplasmic MICAL2 and/or total MICAL2 expression le...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2020.04.019
更新日期:2020-07-28 00:00:00
abstract::Pancreatic cancer is a malignant disease without efficient treatment. Improved treatments are urgently needed to enhance or replace chemotherapy. Here we used a small molecular compound LB-100 to assess the effect of pharmacological inhibition of protein phosphatase 2A (PP2A) in combination with doxorubicin on the pro...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2014.09.048
更新日期:2014-12-28 00:00:00
abstract::Increased abundance of the mRNA-binding protein human antigen R (HuR) is a characteristic feature of many cancers and frequently associated with a high grade malignancy and therapy resistance. HuR elicits a broad cell survival program mainly by stabilizing or increasing the translation of mRNAs coding for anti-apoptot...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2017.02.010
更新日期:2017-05-01 00:00:00
abstract::Tyrosine kinase inhibitor (TKI) treatment is the first-line therapy for non-small cell lung cancer (NSCLC) caused by activating mutations of epidermal growth factor receptor (EGFR). However, acquired resistance to EGFR-TKI occurs almost inevitably. Aberrant activation of proto-oncogene MET has been known to confer EGF...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2020.09.003
更新日期:2020-12-28 00:00:00
abstract::In esophageal squamous cell carcinoma (SCC), we used immunohistochemical analysis to further elucidate the correlation of p53 protein expression with clinicopathological factors, as well as with risk factors, such as tobacco smoking, alcohol consumption and a family history of cancer, using odds ratios (ORs). The expr...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/s0304-3835(01)00461-x
更新日期:2001-06-10 00:00:00
abstract::Circular RNAs (circRNAs) are a class of non-coding RNAs that do not have 5' end caps or 3' end poly (A) tails. There are more than one hundred thousand genes that encode circRNAs. Clinical data show that there are differences in the expression of circRNAs in a variety of diseases, including cancer, suggesting that cir...
journal_title:Cancer letters
pub_type: 杂志文章,评审
doi:10.1016/j.canlet.2018.03.035
更新日期:2018-07-01 00:00:00
abstract::The cell transforming ability of asbestos dust was investigated using C3H10T 1/2 murine fibroblasts. In a series of experiments both crocidolite and amosite caused no increase in the number of transformed foci over that seen in cultures from untreated cells. The dusts, were, however, capable of augmenting the oncogeni...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(83)90071-x
更新日期:1983-03-01 00:00:00
abstract::Inhibition of DNA synthesis was observed and quantitated in hamster buccal pouch epithelium exposed in vivo and in vitro to indirect acting carcinogens. Topical application of a 0.5% solution of the potent hamster buccal pouch carcinogen 7,12-dimethylbenz[a]-anthracene (DMBA) acutely inhibited epithelial DNA synthesis...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/0304-3835(90)90210-o
更新日期:1990-09-01 00:00:00
abstract::Overexpression of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) is implicated in drug resistance and progression of multiple myeloma (MM). The basis for MARCKS induction and impact on MM are not known. Here we show that microRNA-34a (miR-34a), regulates MARCKS translation and is under-expressed in drug-resist...
journal_title:Cancer letters
pub_type: 杂志文章
doi:10.1016/j.canlet.2020.03.020
更新日期:2020-06-28 00:00:00