Inhibition of protein phosphatase 2A sensitizes pancreatic cancer to chemotherapy by increasing drug perfusion via HIF-1α-VEGF mediated angiogenesis.

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 proliferation of pancreatic cancer in cell lines and a xenograft model. LB-100 moderately reduced PP2A activity and the growth of the cell lines but did not show chemosensitization in vitro. In vivo, however, LB-100 synergistically enhanced the activity of doxorubicin. This effect was associated with increased microvessel density, blood perfusion, and doxorubicin concentrations within the xenografts. Mechanically, LB-100 induced expression of hypoxia-induced factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). In an umbilical vein endothelial cell monolayer model for measuring changes in vascular permeability, increased VEGF secretion following exposure to LB-100 and doxorubicin was accompanied by increased amounts of doxorubicin penetrating the endothelial barrier. In conclusion, PP2A inhibition by LB-100 enhanced the cytotoxicity of doxorubicin in vivo but not in vitro potentially via HIF-1α-VEGF mediated angiogenesis. Combining inhibition of PP2A with chemotherapeutic regimens may enhance their effectiveness against pancreatic cancer.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Bai X,Zhi X,Zhang Q,Liang F,Chen W,Liang C,Hu Q,Sun X,Zhuang Z,Liang T

doi

10.1016/j.canlet.2014.09.048

subject

Has Abstract

pub_date

2014-12-28 00:00:00

pages

281-7

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(14)00589-8

journal_volume

355

pub_type

杂志文章
  • Carcinogenicity examination of quercetin and rutin in ACI rats.

    abstract::Carcinogenicity of quercetin and rutin were examined in inbred ACI strain rats. Rats were given a diet containing 1% or 5% quercetin or 5% rutin for 540 days, or 10% quercetin and 10% rutin for 850 days. Rats in control groups were fed a normal basal diet. Most tumors found in experimental groups were also found in th...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(81)90081-1

    authors: Hirono I,Ueno I,Hosaka S,Takanashi H,Matsushima T,Sugimura T,Natori S

    更新日期:1981-06-01 00:00:00

  • Competitive uptake of porphyrin and LDL via the LDL receptor in glioma cell lines: flow cytometric analysis.

    abstract::We examined the simultaneous uptake of porphyrin and (LDL) by four established cell lines of glioma and normal fibroblasts using flow cytometry (FCM). The results indicated porphyrin and LDL showed competitive conjugation with the LDL receptor. These results support the theory of the porphyrin uptake via the LDL recep...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(00)00717-5

    authors: Shibata Y,Matsumura A,Yoshida F,Yamamoto T,Nakai K,Nose T,Sakata I,Nakajima S

    更新日期:2001-05-10 00:00:00

  • Nelfinavir, an HIV protease inhibitor, induces apoptosis and cell cycle arrest in human cervical cancer cells via the ROS-dependent mitochondrial pathway.

    abstract::HIV protease inhibitors (HIV-PIs) are a class of antiretroviral drugs designed to target the viral protease. Strikingly, these drugs have also been reported to possess antitumor effect. In this study, we evaluated the activity of one HIV-PI, Nelfinavir, against human cervical cancer cells. We found that Nelfinavir inh...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2015.04.027

    authors: Xiang T,Du L,Pham P,Zhu B,Jiang S

    更新日期:2015-08-01 00:00:00

  • Effect of later treatment with estrogen on reproductive tract lesions in neonatally estrogenized female mice.

    abstract::Continuous ethinyl estradiol treatment following ovariectomy at day 38 of BALB/cfC3H mice treated neonatally with estradiol resulted in a more organized vaginal epithelium than that seen in the absence of postnatal estrogen, 30 days after treatment was initiated. Although the epithelium became increasingly disorganize...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(82)90023-4

    authors: Wong LM,Bern HA,Jones LA,Mills KT

    更新日期:1982-11-01 00:00:00

  • Epigenetic silencing of chemokine CCL2 represses macrophage infiltration to potentiate tumor development in small cell lung cancer.

    abstract::Highly invasive and rapidly fatal, small-cell lung cancer (SCLC) has been an insurmountable gulf since discovery. Innate immunity plays a vital role in anti-tumor response, among which macrophages contribute to an indispensable character. Here, we found that macrophage infiltration in SCLC reduced significantly in a s...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2020.11.034

    authors: Zheng Y,Wang Z,Wei S,Liu Z,Chen G

    更新日期:2021-02-28 00:00:00

  • Effects of green tea catechins on the progression or late promotion stage of mammary gland carcinogenesis in female Sprague-Dawley rats pretreated with 7,12-dimethylbenz(a)anthracene.

    abstract::Effects of the green tea catechins (GTCs) on the late promotion or progression stage of mammary gland carcinogenesis were examined in female Sprague-Dawley (SD) rats pretreated with 7,12-dimethylbenz(a)anthracene (DMBA). A total of 84 7-week-old rats received a 50 mg/kg body weight intra-gastric dose of DMBA, and star...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(96)04560-0

    authors: Hirose M,Mizoguchi Y,Yaono M,Tanaka H,Yamaguchi T,Shirai T

    更新日期:1997-01-30 00:00:00

  • Immunization with liposome-anchored pegylated peptides modulates doxorubicin sensitivity in P-glycoprotein-expressing P388 cells.

    abstract::The clinical use of chemotherapy in cancer treatment is limited by the occurrence of multidrug resistance (MDR) associated with the overexpression of membrane transporters, one of the best known is P-glycoprotein (Pgp), that actively expels drugs out of tumor cells. To overcome Pgp-mediated MDR, synthetic peptides cor...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2007.04.001

    authors: Gatouillat G,Odot J,Balasse E,Nicolau C,Tosi PF,Hickman DT,López-Deber MP,Madoulet C

    更新日期:2007-11-18 00:00:00

  • Arsenic trioxide-mediated Notch pathway inhibition depletes the cancer stem-like cell population in gliomas.

    abstract::Cancer stem-like cells (CSLCs) are potential targets for treatment of glioblastoma multiforme (GBM) due to their role in tumorigenesis and recurrence. In this study, we investigated the inhibitory effect of arsenic trioxide (As(2)O(3)) on CSLCs of GBM in human glioma cell lines (U87MG, U251MG and U373MG) in vivo and i...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2009.11.005

    authors: Zhen Y,Zhao S,Li Q,Li Y,Kawamoto K

    更新日期:2010-06-01 00:00:00

  • PTK2 promotes cancer stem cell traits in hepatocellular carcinoma by activating Wnt/β-catenin signaling.

    abstract::Emerging evidence indicates that cancer stem cells (CSCs) are involved in tumorigenesis, tumor recurrence, and therapeutic resistance in hepatocellular carcinoma (HCC). However, the mechanisms underlying HCC CSC regulation remain largely unknown. Here we report our analysis of 97 paraffin-embedded HCC tumor specimens....

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2019.02.040

    authors: Fan Z,Duan J,Wang L,Xiao S,Li L,Yan X,Yao W,Wu L,Zhang S,Zhang Y,Li Y,Zhu X,Hu Y,Zhang D,Jiao S,Xu X

    更新日期:2019-05-28 00:00:00

  • MICAL2 is a novel nucleocytoplasmic shuttling protein promoting cancer invasion and growth of lung adenocarcinoma.

    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

    authors: Zhou W,Liu Y,Gao Y,Cheng Y,Chang R,Li X,Zhou Y,Wang S,Liang L,Duan C,Zhang C

    更新日期:2020-07-28 00:00:00

  • Induction of apoptosis in prostate cancer cell lines by the green tea component, (-)-epigallocatechin-3-gallate.

    abstract::Green tea components exert many biological effects, including antitumor and cancer preventive activities. In the search for anticancer agents for prostate cancer the inhibitory effects of green tea components were tested on the prostate cancer cell lines LNCaP, PC-3 and DU145. (-)-Epigallocatechin-3-gallate (EGCG) pro...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(98)00084-6

    authors: Paschka AG,Butler R,Young CY

    更新日期:1998-08-14 00:00:00

  • Cyclic nucleotide concentrations in 1,2-dimethylhydrazine induced rat colon adenocarcinoma.

    abstract::The intracellular concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) in colonic tumors induced in adult male Holtzman rats by 1,2-dimethylhydrazine (DMH) were found to be 1/2 the concentration found in normal large bowel tissue. Intracellular concentrations of guanosine 3'-5'-cyclic monophosphate (cGMP) in ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(78)93192-0

    authors: Stevens RH,Loven DP,Osborne JW,Prall JP,Lawson AJ

    更新日期:1978-01-01 00:00:00

  • MiR-193a-3p promotes the multi-chemoresistance of bladder cancer by targeting the HOXC9 gene.

    abstract::Chemoresistance prevents the curative cancer chemotherapy and presents a formidable challenge for both cancer researchers and clinicians. We have previously shown that miR-193a-3p promotes the multi-chemoresistance of bladder cancer cells via repressing its three target genes: SRSF2, PLAU and HIC2. Here, we showed tha...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2014.11.002

    authors: Lv L,Li Y,Deng H,Zhang C,Pu Y,Qian L,Xiao J,Zhao W,Liu Q,Zhang D,Wang Y,Zhang H,He Y,Zhu J

    更新日期:2015-02-01 00:00:00

  • Mechanisms regulating glioma invasion.

    abstract::Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. GBM poses several unique challenges to currently available treatments...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.canlet.2015.03.015

    authors: Paw I,Carpenter RC,Watabe K,Debinski W,Lo HW

    更新日期:2015-06-28 00:00:00

  • Inhibition of cell transformation by sulindac sulfide is confined to specific oncogenic pathways.

    abstract::Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer (CRC). They are also known to induce the regression of colorectal adenomas, which are precursors to CRC. Despite these evidences, the exact mechanism by which NSAIDs exerts its anti-oncogenic effect is not completely...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(01)00716-9

    authors: Gala M,Sun R,Yang VW

    更新日期:2002-01-10 00:00:00

  • Oncolytic adenovirus expressing relaxin (YDC002) enhances therapeutic efficacy of gemcitabine against pancreatic cancer.

    abstract::Pancreatic cancer is a highly lethal disease for which limited therapeutic options are available. Pancreatic cancer exhibits a pronounced collagen-rich stromal reaction, which induces chemoresistance by inhibiting drug diffusion into the tumor. Complementary treatment with oncolytic virus such as an oncolytic adenovir...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2017.03.009

    authors: Jung KH,Choi IK,Lee HS,Yan HH,Son MK,Ahn HM,Hong J,Yun CO,Hong SS

    更新日期:2017-06-28 00:00:00

  • Hypoxia, hypoxia-inducible gene 2 (HIG2)/HILPDA, and intracellular lipolysis in cancer.

    abstract::Tumor tissues are chronically exposed to hypoxia owing to aberrant vascularity. Hypoxia induces metabolic alterations in cancer, thereby promoting aggressive malignancy and metastasis. While previous efforts largely focused on adaptive responses in glucose and glutamine metabolism, recent studies have begun to yield i...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2020.06.013

    authors: Povero D,Johnson SM,Liu J

    更新日期:2020-11-28 00:00:00

  • Urinary excretion of N-nitrosodiethanolamine administered orally to rats.

    abstract::N-Nitrosodiethanolamine (NDE1A) was administered by gavage to male rats in single doses of 1000, 500 and 100 mg/kg body wt. More than 70% of a given dose was excreted unchanged in the urine, essentially within the first 24 h after exposure. This high excretion rate might explain the relatively low carcinogenic potenti...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(78)94512-3

    authors: Preussmann R,Würtele G,Eisenbrand G,Spiegelhalder B

    更新日期:1978-04-01 00:00:00

  • HGF/c-Met pathway is one of the mediators of sunitinib-induced tumor cell type-dependent metastasis.

    abstract::Recent studies in several tumor models indicated that treatment with angiogenic inhibitors may trigger induction of metastasis to other organs. Here we investigated modes of resistance and invasion in several tumor cell lines including 4T1 (breast), H460 (lung) and Colo205 (colorectal) using sunitinib at doses compara...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2012.01.026

    authors: Shojaei F,Simmons BH,Lee JH,Lappin PB,Christensen JG

    更新日期:2012-07-01 00:00:00

  • 5-(3-Hydroxymethyl-3-methyl-1-triazeno imidazole-4-carboxamide is a metabolite of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC, DTIC NSC-45388).

    abstract::The cancer chemotherapeutic drug, 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (DIC, DTIC, NSC-45388), is metabolised in rats to a structurally related product which was detected by thin-layer chromatography. The novel metabolite has a lower mobility and a colour reaction that is indistinguishable from the pare...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(80)90076-2

    authors: Kolar GF,Maurer M,Wildschütte M

    更新日期:1980-09-01 00:00:00

  • Soluble and membrane-bound catechol-O-methyltransferase in normal and malignant mammary gland.

    abstract::The levels of 26 kDa-soluble (S) and 30 kDa-membrane-bound (MB) catechol-O-methyltransferase (COMT) polypeptides were determined in paired samples from normal and neoplastic breast tissue of 32 patients with breast cancer. Immunohistochemical staining showed that the COMT reaction in normal mammary tissue was restrict...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(99)00197-4

    authors: Tenhunen J,Heikkilä P,Alanko A,Heinonen E,Akkila J,Ulmanen I

    更新日期:1999-09-20 00:00:00

  • Long noncoding RNAs as potential biomarkers in gastric cancer: Opportunities and challenges.

    abstract::Gastric cancer (GC) is a major threat to human health, and its prognosis is poor due to the lack of appropriate biomarkers. LncRNAs are a group of non-protein-coding RNAs that regulate gene expression at the transcriptional or posttranscriptional level. LncRNAs play essential roles in GC initiation and development in ...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2015.11.011

    authors: Yang Z,Guo X,Li G,Shi Y,Li L

    更新日期:2016-02-01 00:00:00

  • Cellular uptake and photosensitizing properties of hematoporphyrin di-ethers with similar chromatographic properties as the tumorlocalizing fraction of hematoporphyrin derivative.

    abstract::The di-methyl-, di-ethyl-, di-propyl-, di-normal butyl-, and di-iso-butyl-ethers of hematoporphyrin were synthesized and shown to possess chromatographic properties similar to those of the tumorlocalizing components of hematoporphyrin derivative (Hpd). The cellular uptake of these ethers, as well as their retention in...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(87)90178-9

    authors: Moan J,Rimington C,Sommer S

    更新日期:1987-03-01 00:00:00

  • Inhibitory effects of triptogelin A-1 on 12-O-tetradecanoylphorbol-13- acetate-induced skin tumor promotion.

    abstract::Dihydroagarofuran sesquiterpenes, which were isolated from Tripterygium wilfordii Hook fil. var. regelii Makino and Euonymus sieboldianus Blume, showed inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Triptogelin A-1, one of the active di...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(93)90138-y

    authors: Ujita K,Takaishi Y,Tokuda H,Nishino H,Iwashima A,Fujita T

    更新日期:1993-02-01 00:00:00

  • Unraveling the roles of Atg4 proteases from autophagy modulation to targeted cancer therapy.

    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

    authors: Zhang L,Li J,Ouyang L,Liu B,Cheng Y

    更新日期:2016-04-01 00:00:00

  • Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL tyrosine phosphatases.

    abstract::Human PRL-1, PRL-2, and PRL-3 tyrosine phosphatases induce the malignant transformation of epithelial cells. We tested the hypothesis that the oncogenic effects of PRL occur by increasing cellular proliferation. Cells stably transfected with PRL-1 or PRL-2 exhibited 2.7-3.3-fold increases over control cells in the rat...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(03)00517-2

    authors: Werner SR,Lee PA,DeCamp MW,Crowell DN,Randall SK,Crowell PL

    更新日期:2003-12-30 00:00:00

  • Absence of ras gene mutations in UV-induced malignant melanomas correlates with a dermal origin of melanocytes in Monodelphis domestica.

    abstract::The South American opossum, Monodelphis domestica, has been used as a model system to study ultraviolet (UV)-induced genetic alterations that lead to the development of melanoma. Suckling young of Monodelphis exposed to multiple doses of UVB radiation can develop benign or malignant melanomas later as adults. Point mu...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/s0304-3835(01)00783-2

    authors: Chan J,Robinson ES,Yeh IT,McCarrey JR

    更新日期:2002-10-08 00:00:00

  • An in vitro model of neoplastic progression in murine epithelial cells.

    abstract::We have developed an epithelial cell line derived from mouse liver which represents a spectrum of malignant progression. When inoculated into mice at low passage, the cells induced benign cysts; after extensive subcultures, the same line induced low grade adenocarcinomas. A variant of these cells with increased invasi...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/0304-3835(80)90102-0

    authors: Dollbaum CM,Anderson LW,Smith HS

    更新日期:1980-12-01 00:00:00

  • NRF2 antioxidant response protects against acidic bile salts-induced oxidative stress and DNA damage in esophageal cells.

    abstract::Gastroesophageal reflux disease (GERD) is the main risk factor for Barrett's tumorigenesis. In this study, we investigated the role of NRF2 in response to exposure to acidic bile salts (ABS), in conditions that mimic GERD, using Barrett's esophagus cell models. We detected an increase in NRF2 protein levels, following...

    journal_title:Cancer letters

    pub_type: 杂志文章

    doi:10.1016/j.canlet.2019.05.031

    authors: Peng D,Lu H,Zhu S,Zhou Z,Hu T,Chen Z,Zaika A,El-Rifai W

    更新日期:2019-08-28 00:00:00

  • Comprehensive genomics linking between neural development and cancer: neuroblastoma as a model.

    abstract::Cancer cells are derived from their precursor cells, which normally develop to the matured cells to form individual organs. Neuroblastoma, one of the most common pediatric solid tumors, originates from possible cancer stem cells derived from the neural crest. During the development, neural crest cells segregate into s...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审

    doi:10.1016/S0304-3835(03)00457-9

    authors: Nakagawara A,Ohira M

    更新日期:2004-02-20 00:00:00