Targeting of MCT1 and PFKFB3 influences cell proliferation and apoptosis in bladder cancer by altering the tumor microenvironment

Hu,Ke Yao; Wang,De Gui; Liu,Peng Fei; Cao,Yan Wei; Wang,Yong Hua; Yang,Xue Cheng; Hu,Cheng Xia; Sun,Li Jiang; Niu,Hai Tao

doi:10.3892/or.2016.4884

Targeting of MCT1 and PFKFB3 influences cell proliferation and apoptosis in bladder cancer by altering the tumor microenvironment

Authors:
- Ke Yao Hu
- De Gui Wang
- Peng Fei Liu
- Yan Wei Cao
- Yong Hua Wang
- Xue Cheng Yang
- Cheng Xia Hu
- Li Jiang Sun
- Hai Tao Niu
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Affiliations: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266101, P.R. China, Department of Anatomy, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Pain Treatment, Haiyang Hospital of The Affiliated Hospital of Qingdao University, Haiyang, Shandong 265100, P.R. China
Published online on: June 16, 2016 https://doi.org/10.3892/or.2016.4884
Pages: 945-951

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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.

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