title: SET protein overexpression contributes to paclitaxel resistance in MCF-7/S cells through PI3K/Akt pathway.
abstract: Patient SE translation (SET) is a carcinogen in facilitating cellular growth and proliferation, and promoting tumorigenesis and metastasis. The present study was to investigate the resistance mechanisms associated with SET in paclitaxel-induced human breast cancer cells. The different expressions of SET, ATP-binding cassette (ABC) transporters and PI3K/Akt pathway between paclitaxel sensitive MCF-7/S and paclitaxel resistant MCF-7/PTX cells were identified using western blotting. We adopted plasmid transfection to upregulate SET in MCF-7/S cells and a novel SET antagonist COG112 to decrease SET in MCF-7/PTX cells. Subsequently, cell viability to paclitaxel was assessed by MTT assay and cell apoptosis was analyzed by flow cytometry. We found that levels of SET, ABC transporters and PI3K/Akt pathway were elevated in MCF-7/PTX. Upregulation of SET in MCF-7/S cells expressed resistant to paclitaxel and decreased cell apoptosis. Moreover, overexpression of SET promoted the mRNA and protein level of ABC transporters and PI3K/Akt signal pathway in MCF-7/S cells. Conversely, decreased level of SET by COG112 not only significantly sensitized MCF-7/PTX cells to paclitaxel, but also enhanced paclitaxel-induced cell apoptosis. Additionally, the levels of the ABC transporters and PI3K/Akt signal pathway were also reduced in the COG112-treated MCF-7/PTX cells. The above results demonstrated that SET was associated with paclitaxel resistance in MCF-7/PTX cells.
authors.affiliation: a Department of Pharmacy , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , PR China.|b Department of Pharmacy , The Eighth Hospital of Xi'an , Xi'an , PR China.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: a Department of Pharmacy , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , PR China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zheng
authors.affiliation: a Department of Pharmacy , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , PR China.
authors.forename: Ti
authors.initials: T
authors.lastname: Meng
authors.affiliation: a Department of Pharmacy , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , PR China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: You
authors.affiliation: a Department of Pharmacy , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , PR China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Dong
authors.affiliation: c School of Pharmacy, Xi'an Jiaotong University , Xi'an , PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xing
authors.affiliation: a Department of Pharmacy , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , PR China.
authors.forename: Siying
authors.initials: S
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D056488:Histone Chaperones / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D017239:Paclitaxel / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D017239:Paclitaxel; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; C513473:SET protein, human
keywords: ABC transporters; Breast cancer; PI3K/Akt; SET; paclitaxel resistance