title: Stanniocalcin 2 induces oxaliplatin resistance in colorectal cancer cells by upregulating P-glycoprotein.
abstract: Multidrug resistance (MDR) limits the anticancer effects of chemotherapy in patients with metastatic colorectal cancer (CRC). Oxaliplatin is a common component of combinational therapeutic regimens administered to patients with metastatic CRC; however, it is also used as a constituent of adjuvant therapy for patients at a risk of recurrent disease. In the present study, we investigated the role of stanniocalcin 2 (STC2) in chemoresistance. STC2 knockdown sensitized chemoresistant CRC cells to oxaliplatin. Moreover, the expression of exogenous STC2 in chemonaïve CRC cells induced oxaliplatin resistance. We confirmed that STC2 upregulated P-glycoprotein (P-gp) expression in CRC cells. Furthermore, shRNA against phosphoinositide 3-kinase (PI3K) or Akt inhibited the action of STC2 on P-gp upregulation and MDR in CRC. To our knowledge, this is the first report to demonstrate the induction of oxaliplatin resistance in CRC cells in response to STC2 stimulation of P-gp via the PI3K/Akt signaling pathway.
authors.affiliation: a Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.|c Drug Research Base of Cardiovascular and Cerebral Vascular, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: a Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhan
authors.affiliation: b Department of Histology and Embryology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: d Department of Immunology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Jiang
authors.affiliation: a Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.|c Drug Research Base of Cardiovascular and Cerebral Vascular, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors.forename: Xia-Min
authors.initials: XM
authors.lastname: Hu
authors.affiliation: b Department of Histology and Embryology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China.
authors.forename: Xin-Chu
authors.initials: XC
authors.lastname: Yuan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009944:Organoplatinum Compounds; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; C114997:STC2 protein, human; D000077150:Oxaliplatin; D051057:Proto-Oncogene Proteins c-akt
keywords: P-glycoprotein; glycoprotéine P; multidrug resistance; multirésistance aux médicaments; oxaliplatin; oxaliplatine; phosphoinositide 3-kinase/Akt; stanniocalcin 2; stanniocalcine 2