Significant anti-proliferation of human endometrial cancer cells by combined treatment with a selective COX-2 inhibitor NS398 and specific MEK inhibitor U0126

Gao, Jingchun; Niwa, Koichiro; Takemura, Masao; Sun, Wen-Shu; Onogi, Kyoko; Wu, Yun; Seishima, Mitsuru; Mori, Hideki; Tamaya, Teruhiko

doi:10.3892/ijo.26.3.737

Cited by 17 publications

(19 citation statements)

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“…In vitro, aspirin and NSAIDs have been reported to inhibit proliferation in EC cells [139][140][141][142][143][144]. Given the critical role of Wnt signaling in the regulation of cell proliferation, an association between the inhibition of endometrial proliferation by NSAIDs and Wnt signaling could be hypothesized, although such association has not been elucidated yet.…”

Section: Reviewmentioning

confidence: 99%

Role of canonical Wnt signaling in endometrial carcinogenesis

Dellinger

Planutis

Tewari

et al. 2012

Expert Review of Anticancer Therapy

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While the role of Wnt signaling is well established in colorectal carcinogenesis, its function in gynecologic cancers has not been elucidated. Here, we describe the current state of knowledge of canonical Wnt signaling in endometrial cancer (EC), and its implications for future therapeutic targets. Deregulation of the Wnt/b-catenin signaling pathway in EC occurs by inactivating b-catenin mutations in approximately 10-45% of ECs, and via downregulation of Wnt antagonists by epigenetic silencing. The Wnt pathway is intimately involved with estrogen and progesterone, and emerging data implicate it in other important signaling pathways, such as mTOR and Hedgehog. While no therapeutic agents targeting the Wnt signaling pathway are currently in clinical trials, the preclinical data presented suggest a role for Wnt signaling in uterine carcinogenesis, with further research warranted to elucidate the mechanism of action and to proceed towards targeted cancer drug development.

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Section: Reviewmentioning

confidence: 99%

Role of canonical Wnt signaling in endometrial carcinogenesis

Dellinger

Planutis

Tewari

et al. 2012

Expert Review of Anticancer Therapy

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“…And several combination therapies have been reported, such as MEK inhibitor with PPARγ ligands [9], nonsteroidal anti-inflammatory drugs (NSAIDs) [10], and some anticancer drugs [11,12]. These observations predict that MEK inhibitors may increase the sensitivity of cancer cells to some chemotherapeutic agents.…”

Section: Introductionmentioning

confidence: 98%

MEK Activation Suppresses CPT11-Induced Apoptosis in Rat Intestinal Epithelial Cells Through a COX-2-Dependent Mechanism

et al. 2007

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Resistance to chemotherapeutic agents is one of the distinct features of cancer cells. We evaluate the role of activated MEK-ERK signaling in Camptotecin/irinotecan (CPT-11)-induced cell death using constitutively activated MEK1-transfected normal rat intestinal epithelial cells (IEC-caMEK cells). A CPT-11-induced inhibitory concentration of 50% was determined by WST assay. Apoptosis was evaluated by DNA staining and fragmented DNA analysis. Protein expressions were analyzed by western blotting. We also examined the role of cyclooxygenase-2 in the cell systems. IEC-caMEK cells possessed survival advantages compared to control cells. Apoptosis was remarkably suppressed in IEC-caMEK cells. Western blot analysis revealed increased expression of Bcl-2, Bcl-xL, Mcl-1, and COX-2 and decreased expression of Bak in IEC-caMEK cells. The COX-2 selective inhibitor ameliorated the antiapoptotic nature of IEC-caMEK cells. MEK activation suppressed CPT-11-induced apoptosis in IEC-caMEK cells via a COX-2- dependent mechanism. Therefore, MEK-ERK signaling may contribute to the drug-resistant nature of cancer cells.

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“…Information regarding the molecular pathways that regulate the anti-proliferative effects of individual NSAIDs is controversial at the present time [3][4][5]. Recent have identified a series of new molecular targets for NSAIDs that are mainly involved in signaling pathways; these include 15-lipoxygenase-1 [6], extracellular signalregulated kinase 1/2 signaling [7], nuclear factor kappaB (NF-_B) [8] and the Akt/PKB kinases [9].…”

Section: Introductionmentioning

confidence: 99%

The COX-2 Selective Inhibitor-Independent COX-2 Effect on Colon Carcinoma Cells is Associated with the Delta1/Notch1 Pathway

Zhang

Bai

et al. 2008

Dig Dis Sci

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Our results show that the selective COX-2 inhibitor may inhibit the proliferation and induce apoptosis in colon cancer cells through the COX-2-dependent pathway (HT-29) by decreasing the COX-2 mRNA/PGE2 levels and the activity of the COX-2-independent pathway (SW480). The Notch1 signal pathway mediates the effects of the COX-2 inhibitor on the proliferation and apoptosis of colon cancer cells. This may be a new target of the selective COX-2 inhibitor effect on colon cancer.

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Significant anti-proliferation of human endometrial cancer cells by combined treatment with a selective COX-2 inhibitor NS398 and specific MEK inhibitor U0126

Cited by 17 publications

References 0 publications

Role of canonical Wnt signaling in endometrial carcinogenesis

Role of canonical Wnt signaling in endometrial carcinogenesis

MEK Activation Suppresses CPT11-Induced Apoptosis in Rat Intestinal Epithelial Cells Through a COX-2-Dependent Mechanism

The COX-2 Selective Inhibitor-Independent COX-2 Effect on Colon Carcinoma Cells is Associated with the Delta1/Notch1 Pathway

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