TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000219476
  • Gene Name:TSC2
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:PI3K/Akt/mTOR signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:12-Deoxyphorbol 13-palmitate
  • Drug Method:up-regulated the gene expression

Disease basic infommation

  • Disease:breast cancer
  • Tissue:cell line (MCF-7)

Other information

  • Title:12-Deoxyphorbol 13-palmitate inhibits the expression of VEGF and HIF-1alpha in MCF-7 cells by blocking the PI3K/Akt/mTOR signaling pathway
  • Journal:Oncol Rep
  • Published:2015
  • PubMed ID:26239613
  • Abstract:Vascular endothelial growth factor (VEGF) is an essential component for angiogenesis, and hypoxia-inducible factor-1α (HIF-1α), which controls the switch of glycolytic and oxidative metabolism, activates the transcription of VEGF. 12-Deoxyphorbol 13-palmitate (DP) is a compound isolated from the roots of Euphorbia fischeriana, and has been revealed to possess anticancer activity. In the present study, we found that DP is an effective inhibitor of VEGF and HIF-1α in MCF-7 cells. DP markedly reduced cell viability as determined by MTT assay. ELISA, western blotting and RT-qPCR assays indicated that DP significantly decreased the protein and mRNA expression of VEGF and the protein expression of HIF-1α, while HIF-1α mRNA remained unchanged. In addition, the entrance of HIF-1α into the nucleus was blocked after DP treatment as detected by immunofluorescence analysis. In a further study, we proved that the effects mentioned above were associated with constitutive interference of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. DP effectively inhibited the phosphorylation of PI3K and its downstream factors p-Akt and p-mTOR, oppositely enhanced the expression of TSC1 (hamartin) and TSC2 (tuberin), which could be reversed by the co-treatment with the PI3K inhibitor wortmannin. Moreover, the addition of wortmanin further downregulated the protein levels of VEGF and HIF-1α. The results revealed that DP inhibited the expression of VEGF and HIF-1α through the PI3K/Akt/mTOR signaling pathway, confirming that DP may be a potential therapeutic candidate for breast cancer.
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