Combination treatment of PD98059 and DAPT in gastric cancer through induction of apoptosis and downregulation of WNT/β-catenin

Yao, Jun; Qian, Cheng; Shu, Ting; Zhang, Xin; Zhao, Zhiqiang; Liang, Yong

doi:10.4161/cbt.25332

Cited by 34 publications

(25 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). Consistent with this extensive interwoven network, various small-molecule inhibitors of these pathways, including inhibitors of Notch and the mitogen-activated protein kinase (MAPK) pathway 185,186 , indirectly affect WNT signalling. The WNT and RAS signalling cascades have been observed to synergistically contribute to tumour initiation and development in a number of transgenic mouse tumour models, including colon 187 , intestine 188 and liver 189 tumours.…”

Section: Crosstalk With the Wnt Pathwaymentioning

confidence: 91%

Can we safely target the WNT pathway?

Kahn

2014

Nat Rev Drug Discov

911

858

View full text Add to dashboard Cite

WNT–β-catenin signalling is involved in a multitude of developmental processes and the maintenance of adult tissue homeostasis by regulating cell proliferation, differentiation, migration, genetic stability and apoptosis, as well as by maintaining adult stem cells in a pluripotent state. Not surprisingly, aberrant regulation of this pathway is therefore associated with a variety of diseases, including cancer, fibrosis and neurodegeneration. Despite this knowledge, therapeutic agents specifically targeting the WNT pathway have only recently entered clinical trials and none has yet been approved. This Review examines the problems and potential solutions to this vexing situation and attempts to bring them into perspective.

show abstract

Section: Crosstalk With the Wnt Pathwaymentioning

confidence: 91%

Can we safely target the WNT pathway?

Kahn

2014

Nat Rev Drug Discov

911

858

View full text Add to dashboard Cite

show abstract

“…LRP6 phosphorylation is accompanied by receptor internalization in caveolin-containing vesicles and endocytosis, which is essential for Wnt/b-catenin signaling [250] . Yao et al [251] observed that the combined treatment with the ERK1/2 inhibitor PD98059 and the γ-secretase inhibitor DAPT in gastric cancer originated induction of apoptosis and regulation of b-catenin, c-Myc, and cyclin D1. Although this combined treatment results in a dramatically increased cytotoxicity compared to that observed with any of the drugs alone, the exact mechanism by which these two agents act together to downregulate Wnt/b-catenin signaling pathway remains unknown.…”

Section: Targeting the Wnt/b-catenin Pathway As Potential Therapy In mentioning

confidence: 99%

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

Chiurillo

2015

WJEM

270

219

View full text Add to dashboard Cite

Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput "omics" approaches will help in the search for Wnt pathway antagonist in the near future.

show abstract

“…DAPT can inhibit the mRNA expression of Notch pathway-related genes (Notch1, Notch2, and Dll1) [17]. Although DAPT is not a specific inhibitor of the Notch pathway, and has a broad impact on other transduction pathways such as the Wnt pathway [18] and PI3K/Akt pathway [19], many studies have used DAPT to elucidate the functions of the Notch pathway.…”

mentioning

confidence: 99%

Inhibition of the Notch Signaling Pathway Reduces the Differentiation of Hepatic Progenitor Cells into Cholangiocytes in Biliary Atresia

Mao

Tang

Yang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Viral infections, especially with rotavirus, are often considered an initiator of the pathogenesis of biliary atresia (BA). However, the mechanism by which rotavirus induces BA is still unclear. Methods: A BA mouse model was induced in newborn mice by i.p. inoculation with rhesus rotavirus within 6 h of birth. The expression of Notch pathway-associated molecules (JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, DII1, DII3, and DII4) was measured by quantitative PCR and western blot analysis. Bile duct obstruction was detected by hematoxylin and eosin staining and CK-19 immunohistochemical staining. DAPT was used to inhibit the Notch pathway in vivo and in vitro. Results: In the livers of patients with BA and rotavirus-induced BA mice, the expression of JAG1 and Notch2 was significantly increased. Inhibition of the Notch pathway by DAPT in vivo ameliorated bile duct obstruction and delayed BA-induced mortality. The serum levels of inflammation cytokines (TNF-α, IL-2, IL-8, and IL-18) were reduced by inhibiting the Notch pathway. The expression of CK19, Sox9, and EpCAM was significantly increased in BA liver, while DAPT treatment decreased the expression of CK19, Sox9, and EpCAM. Conclusion: Notch activation is involved in the pathogenesis of BA by promoting the differentiation of hepatic progenitor cells into cholangiocytes.

show abstract

Combination treatment of PD98059 and DAPT in gastric cancer through induction of apoptosis and downregulation of WNT/β-catenin

Cited by 34 publications

References 24 publications

Can we safely target the WNT pathway?

Can we safely target the WNT pathway?

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

Inhibition of the Notch Signaling Pathway Reduces the Differentiation of Hepatic Progenitor Cells into Cholangiocytes in Biliary Atresia

Contact Info

Product

Resources

About