title: Targeting of MCT1 and PFKFB3 influences cell proliferation and apoptosis in bladder cancer by altering the tumor microenvironment.
abstract: Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) and monocarboxylate transporter 1 (MCT1) play important roles in tumor endothelial cells (ECs) and several biological processes. The present study was conducted to study the effects of PFKFB3 and MCT1 on cell proliferation and apoptosis in the tumor microenvironment by co-culture of HUVECs and T24, a bladder cancer (BC) cell line, using a microfluidic device. Immunofluorescence assay showed that HUVEC activity was significantly enhanced under co-culture with T24 cells, according to the stronger fluorescence intensity of CD31 and CD105 than that in the signal‑cultured cells. Quercetin treatment inhibited MCT1 expression but did not affect PFKFB3 expression. Knockdown of MCT1 or/and PFKFB3 increased the apoptosis rate of the HUVECs under single-culture and co-culture situations by staining with calcein and propidium iodide. Meanwhile, cell proliferation and lactic concentration were significantly decreased after the blocking of MCT1 or/and PFKFB3, as compared with that in the control group. No obvious differences in the effects on apoptosis, proliferation and lactic concentration were found between cells treated with quercetin and siMCT1. Thus, we concluded that the targeting of MCT1 and PFKFB3 regulated cell proliferation and apoptosis in BC cells by altering the tumor microenvironment, and quercetin exhibited a potential antitumor effect by targeting MCT1.
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266101, P.R. China.
authors.forename: Ke Yao
authors.initials: KY
authors.lastname: Hu
authors.affiliation: Department of Anatomy, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: De Gui
authors.initials: de G
authors.lastname: Wang
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266101, P.R. China.
authors.forename: Peng Fei
authors.initials: PF
authors.lastname: Liu
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266101, P.R. China.
authors.forename: Yan Wei
authors.initials: YW
authors.lastname: Cao
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266101, P.R. China.
authors.forename: Yong Hua
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266101, P.R. China.
authors.forename: Xue Cheng
authors.initials: XC
authors.lastname: Yang
authors.affiliation: Department of Pain Treatment, Haiyang Hospital of The Affiliated Hospital of Qingdao University, Haiyang, Shandong 265100, P.R. China.
authors.forename: Cheng Xia
authors.initials: CX
authors.lastname: Hu
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266101, P.R. China.
authors.forename: Li Jiang
authors.initials: LJ
authors.lastname: Sun
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266101, P.R. China.
authors.forename: Hai Tao
authors.initials: HT
authors.lastname: Niu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D018920:Coculture Techniques / Q000379:methods; D006801:Humans; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D025481:Phosphofructokinase-2 / Q000235:genetics*; D027981:Symporters / Q000235:genetics*; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000970:Antineoplastic Agents; D027501:Monocarboxylic Acid Transporters; D025481:Phosphofructokinase-2; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C107345:PFKFB3 protein, human