Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphoglycerate dehydrogenase (PHGDH) is the key enzyme of de novo serine biosynthesis. Previous reports have demonstrated that PHGDH plays an important role in some malignancies. However, the biological role of PHGDH in human cervical adenocarcinoma has not been explored. We examined the expression of PHGDH in 54 cervical adenocarcinoma samples by immunohistochemistry and evaluated the association with clinicopathological parameters and prognosis. We performed shRNA transfection to knock down PHGDH gene expression in HeLa cells. A cell proliferation test, cisplatin cytotoxicity test and apoptosis test examined the HeLa cell line after PHGDH knockdown in vitro. In vivo tumorigenesis was assessed using a mouse xenograft model. Moreover, we examined the effects on Bcl-2 and cleaved caspase-3 expression after knockdown of PHGDH and treatment of cisplatin for 48h by Western blot. In this study, we demonstrated that elevated PHGDH expression was found in cervical adenocarcinoma and was associated with tumor size and prognosis. Knocking down PHGDH in HeLa cells significantly inhibited cell proliferation and increased cisplatin chemotherapy sensitivity. Silencing PHGDH resulted in inhibition of tumorigenesis in vivo. Furthermore, PHGDH knockdown reduced Bcl-2 and increased cleaved caspase-3 expression. Collectively, our study indicates the novel roles of PHGDH in cervical adenocarcinoma and identifies PHGDH as a new anticancer target.
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PMID:Downregulation of phosphoglycerate dehydrogenase inhibits proliferation and enhances cisplatin sensitivity in cervical adenocarcinoma cells by regulating Bcl-2 and caspase-3. 2571 55

Gastric cancer (GC) is one of the most common malignancies in the world. Fluorouracil (5-FU) is widely used in the treatment of cancers, but resistance to 5-FU results in the failure of chemotherapy. Phosphoglycerate dehydrogenase (PHGDH) has been reported to play a vital role in the development of 5-FU resistance in cancer cells. However, the exact role of PHGDH and the underlying mechanisms for 5-FU resistance in GC cells remain elusive. In this study, PHGDH expression was much higher in the GC tissues of 5-FU-resistant patients than that in the GC tissues of 5-FU-sensitive patients. Moreover, the expression of PHGDH was obviously increased in BGC823/5-FU cells compared with that in BGC823 cells. 5-FU treatment significantly reduced the viability of BGC823/5-FU cells, in a dose- and time-dependent manner. Furthermore, 5-FU treatment inhibited the proliferation of BGC823/5-FU cells, as evidenced by decreased cell viability and reduced colony-forming ability. The knockdown of PHGDH made possible the inhibitory effect of 5-FU on the proliferation of BGC823/5-FU cells. Furthermore, 5-FU treatment promoted apoptosis of BGC823/5-FU cells, as indicated by increased numbers of TUNEL-positive cells and increased rates of apoptosis. Notably, the promoting effect of 5-FU on the apoptosis of BGC823/5-FU cells was markedly enhanced by PHGDH knockdown. Additionally, 5-FU treatment downregulated Bcl-2 expression and upregulated the expression of Bax and caspase-3, and this effect was remarkably enhanced by PHGDH knockdown. In conclusion, knockdown of PHGDH potentiates 5-FU cytotoxicity in GC cells via the Bcl-2/Bax/caspase-3 signaling pathway.
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PMID:Knockdown of PHGDH potentiates 5-FU cytotoxicity in gastric cancer cells via the Bcl-2/Bax/caspase-3 signaling pathway. 3194 73