Author:
Chen Chaojiang,Cai Zhiduan,Zhuo Yangjia,Xi Ming,Lin Zhuoyuan,Jiang Funeng,Liu Zezhen,Wan Yueping,Zheng Yu,Li Jianxin,Zhou Xing,Zhu Jianguo,Zhong Weide
Abstract
Abstract
Background
Solute Carrier Family 6 Member 1 (SLC6A1) has been identified as a cancer-promoting gene in various human cancers, such as clear cell renal cell carcinoma and ovarian cancer. However, its roles in prostate cancer (PCa) has not been fully elucidated. The aim of this study was to investigate the expression and clinical significance of SLC6A1 in PCa tissues and its effect on drug resistance to docetaxel in PCa.
Methods
Expression patterns of SLC6A1 protein in PCa tissues were examined by immunohistochemistry based on Tissue microarray. Associations of SLC6A1 protein expression with various clinicopathological features and patients’ prognosis of PCa were also statistically evaluated based on TCGA data. Roles of SLC6A1 deregulation in prostate carcinogenesis and drug resistance was further determined in vitro and in vivo experiments.
Results
Based on TCGA Dataset, SLC6A1 expression was markedly higher in patients with high Gleason score, advanced clinical stage and positive biochemical recurrence than those with control features (all P < 0.05). Both unvariate and multivariate analyses demonstrated that SLC6A1 expression was significantly associated with biochemical recurrence-free survival in PCa patients. In addition, enforced expression of SLC6A1 effectively promoted cell proliferation, migration and invasion of PCa cells in vitro. Moreover, the inhibition of SLC6A1 suppressed the tumor growth in vivo. Additionally, immunohistochemical notches of PCNA and MMP-9 in the low-expression cluster were pointedly lower compared to those of NC group. Finally, the cell viability revealed that the overexpression of SLC6A1 obviously promoted the PCa cell resistant to docetaxel (DTX), and the transplanted tumor in the overexpression group had no significant reduction compared with the untreated group.
Conclusions
Our data suggest that SLC6A1 overexpression may be associated with aggressive progression and short biochemical recurrence-free survival of PCa, and may be related to the resistance to docetaxel therapy.
Funder
National Natural Science Foundation of China
Science and Technology Project of Guangdong Province
Guangzhou Municipal Science and Technology Project
Natural Science Foundation of Guangdong Province
Medical Scientific Research Foundation of Guangdong Province
The General Guiding Project of Guangzhou Health and Family Planning Commission
Science and Technology Planning Project of Shenzhen Municipality
Science and Technology Project of Guizhou Province in 2017
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Cited by
12 articles.
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