LY294002 Induces G0/G1 Cell Cycle Arrest and Apoptosis of Cancer Stem-like Cells from Human Osteosarcoma Via Down-regulation of PI3K Activity

Chen, Gong; Liao, Hui; Wang, Jiang; Yang, Lin; Qi, Jun; Qin, Liang; Tian, Lei; Guo, Fengjing

doi:10.7314/apjcp.2012.13.7.3103

Cited by 39 publications

(27 citation statements)

References 23 publications

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“…Several studies have demonstrated that alteration of PI3K/AKT/PTEN and Wnt/ β-catenin was found in many cancers and these pathways may serve as the potential targets for cancer treatment (Gong et al, 2012;Pandurangan, 2013;Jannesari-Ladani et al, 2014;Tan et al, 2014). This is the first report of the alteration of the protein components comprising the PI3K/ AKT/PTEN and Wnt/β-catenin pathway in a hamster model of Ov-induced CCA carcinogenesis.…”

Section: Discussionmentioning

confidence: 78%

Opisthorchis viverrini Infection Activates the PI3K/AKT/PTEN and Wnt/β-catenin Signaling Pathways in a Cholangiocarcinogenesis Model

Yothaisong¹,

Thanee²,

Namwat³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Opisthorchis viverrini (Ov) infection is the major etiological factor for cholangiocarcinoma (CCA), especially in northeast Thailand. We have previously reported significant involvement of PI3K/AKT/PTEN and Wnt/β-catenin in human CCA tissues. The present study, therefore, examined the expression and activation of PI3K/ AKT/PTEN and Wnt/β-catenin signaling components during Ov-induced cholangiocarcinogenesis in a hamster animal model. Hamsters were divided into two groups; non-treated and Ov plus NDMA treated. The results of immunohistochemical staining showed an upregulation of PI3K/AKT signaling as determined by elevated expression of the p85α-regulatory and p110α-catalytic subunits of PI3K as well as increased expression and activation of AKT during cholangiocarcinogenesis. Interestingly, the staining intensity of activated AKT (p-AKT) increased in the apical regions of the bile ducts and strong staining was detected where the liver fluke resides. Moreover, PTEN, a negative regulator of PI3K/AKT, was suppressed by decreased expression and increased phosphorylation during cholangiocarcinogenesis. We also detected upregulation of Wnt/β-catenin signaling as determined by increased positive staining of Wnt3, Wnt3a, Wnt5a, Wnt7b and β-catenin, corresponded with the period of cholangiocarcinogenesis. Furthermore, nuclear staining of β-catenin was observed in CCA tissues. Our results suggest the liver fluke infection causes chronic inflammatory conditions which lead to upregulation of the PI3K/AKT and Wnt/β-catenin signaling pathways which may drive CCA carcinogenesis. These results provide useful information for drug development, prevention and treatment of CCA.

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Section: Discussionmentioning

confidence: 78%

Opisthorchis viverrini Infection Activates the PI3K/AKT/PTEN and Wnt/β-catenin Signaling Pathways in a Cholangiocarcinogenesis Model

Yothaisong¹,

Thanee²,

Namwat³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…PI3K activity is known to be involved in cell cycle progression [31, 32]. Because of their differential response profile to GDC-0941 treatment, MEB-Med-8A and Daoy were chosen to assess cell cycle distribution after 48 h of drug treatment (Figure 2C, upper panel).…”

Section: Resultsmentioning

confidence: 99%

The PI3K inhibitor GDC-0941 displays promisingin vitro and in vivoefficacy for targeted medulloblastoma therapy

et al. 2014

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Deregulation of the Phosphoinositide 3-kinase (PI3K)/AKT signalling network is a hallmark of oncogenesis. Also medulloblastoma, the most common malignant brain tumor in children, is characterized by high levels of AKT phosphorylation and activated PI3K signalling in medulloblastoma is associated with enhanced cellular motility, survival and chemoresistency underscoring its role of as a potential therapeutic target. Here we demonstrate that GDC-0941, a highly specific PI3K inhibitor with good clinical tolerability and promising anti-neoplastic activity in adult cancer, also displays anti-proliferative and pro-apoptotic effects in pediatric human medulloblastoma cell lines. Loss in cell viability is accompanied by reduced phosphorylation of AKT, a downstream target of PI3K. Furthermore, we show that GDC-0941 attenuates the migratory capacity of medulloblastoma cells and targets subpopulations expressing the stem cell marker CD133. GDC-0941 also synergizes with the standard medulloblastoma chemotherapeutic etoposide. In an orthotopic xenograft model of the most aggressive human medulloblastoma variant we document that oral adminstration of GDC-0941 impairs tumor growth and significantly prolongs survival. These findings provide a rational to further investigate GDC-0941 alone and in combination with standard chemotherapeutics for medulloblastoma treatment.

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“…The phosphatidylinositol-3-kinase (PI3K)/AKT pathway plays an important role in various cellular processes including cell growth, survival and motility (Vivanco et al, 2002;He et al, 2013;Gong et al, 2012). Recently, accumulating evidence indicated that PI3K/ Akt pathway plays a crucial role in tumorigenesis and tumor progression by promoting cell proliferation and inhibiting apoptosis.…”

Section: Down Regulation Of Pi3k/akt Pathway Induce Anoikis Of Osa Cellsmentioning

confidence: 99%

Review of the Molecular Pathogenesis of Osteosarcoma

Hao²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

124

109

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Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA.

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LY294002 Induces G0/G1 Cell Cycle Arrest and Apoptosis of Cancer Stem-like Cells from Human Osteosarcoma Via Down-regulation of PI3K Activity

Cited by 39 publications

References 23 publications

Opisthorchis viverrini Infection Activates the PI3K/AKT/PTEN and Wnt/β-catenin Signaling Pathways in a Cholangiocarcinogenesis Model

Opisthorchis viverrini Infection Activates the PI3K/AKT/PTEN and Wnt/β-catenin Signaling Pathways in a Cholangiocarcinogenesis Model

The PI3K inhibitor GDC-0941 displays promisingin vitro and in vivoefficacy for targeted medulloblastoma therapy

Review of the Molecular Pathogenesis of Osteosarcoma

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