title: Downregulation of phosphoglycerate dehydrogenase inhibits proliferation and enhances cisplatin sensitivity in cervical adenocarcinoma cells by regulating Bcl-2 and caspase-3.
abstract: 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.
authors.affiliation: a Department of Obstetrics and Gynecology; Shengjing Hospital; China Medical University ; Shenyang , Liaoning , China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Jing
authors.forename: Wei
authors.initials: W
authors.lastname: Heng
authors.forename: Liu
authors.initials: L
authors.lastname: Xia
authors.forename: Wang
authors.initials: W
authors.lastname: Ning
authors.forename: Qi
authors.initials: Q
authors.lastname: Yafei
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yao
authors.forename: Zhang
authors.initials: Z
authors.lastname: Shulan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D050543:Phosphoglycerate Dehydrogenase; D053148:Caspase 3; D002945:Cisplatin
keywords: Bcl-2; Bcl-2, B cell leukemia/lymphoma-2; CCK-8, cell counting kit-8; Caspase, Cysteinyl aspartate specific proteinase; DMEM, Dulbecco's Modified Eagle Medium; FBS, fetal calf serum; G418, Geneticin; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; HPV, human papilloma virus; ICC, immuocytochemistry; IHC, immunohistochemistry; PHGDH; PHGDH, phosphoglycerate dehydrogenase; caspase-3; cervical adenocarcinoma; chemotherapy sensitivity; metabolism; proliferation; shRNA, short hairpin RNA