文献类型：期刊文献

英文题名：Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5-fluorouracil in gastric cancer cells

作者：Liang, Xin[1,2];Shi, Haiyang[1,2];Yang, Liyan[1,2];Qiu, Cen[1,2];Lin, Shengchao[1,2];Qi, Yingxue[1,2];Li, Jiyu[3];Zhao, Aiguang[4];Liu, Jianwen[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, POB 268 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, POB 268 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Tongji Univ, Shanghai Tenth Peoples Hosp, Sch Med, Dept Gen Surg, 301 Yanchang Rd, Shanghai 200072, Peoples R China;[4]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Oncol, 725 South Wanping Rd, Shanghai 200032, Peoples R China

年份：2017

卷号：116

期号：7

起止页码：903

外文期刊名：BRITISH JOURNAL OF CANCER

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000397828800008)】；

基金：This work was supported by National Nature Science Funds of China (NO. 81173224, 81270555, 81373861). We appreciate the help of Professor Zhewei Fei and Mr Wen Xu at Shanghai Xinhua Hospital Affiliated to School of Medicine, Shanghai Jiaotong University in collecting and providing human gastric cancer samples.

语种：英文

外文关键词：PTBP3; apoptosis; cell cycle arrest; 5-FU; gastric cancer

摘要：Background: Human polypyrimidine tract binding protein 3 (PTBP3) was first discovered in 1999 and has been well characterised as a differentiation regulator. However, its role in human cancer has rarely been reported. Our previous study revealed increased PTBP3 protein level in gastric cancer tissues. Downregulation of PTBP3 suppressed the proliferation and differentiation of gastric cancer cells in vivo. Methods: PTBP3 mRNA levels in human gastric cancer and adjuvant non-tumour tissues were detected. Apoptosis and 5-FU effect were determined in PTBP3-silenced gastric cancer cells. Underlying molecular mechanisms were investigated. Results: MRNA expression of PTBP3 was upregulated in gastric cancer tissues, especially in those at an advanced stage. PTBP3 silencing led to apoptosis, under which modulation of PTB and thereby switch of Bcl-x pre-mRNA splicing pattern might be an important mechanism. Further research found that inhibition of PTBP3 expression enhanced the chemosensitivity of gastric cancer cells towards 5-FU treatment. This was mediated by reduced expression of histone deacetylase 6 (HDAC6), which further inhibited the phosphorylation of Akt and the expression of thymidylate synthase (TYMS), the critical determinant of 5-FU cytotoxicity. Conclusions: PTBP3 might serve as a biomarker of gastric cancer or potential target for anti-cancer therapy.