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山东大学学报（医学版） ›› 2017, Vol. 55 ›› Issue (8): 1-6.doi: 10.6040/j.issn.1671-7554.0.2016.378

• 基础医学 •    下一篇

CYLD抑制自噬提高膀胱癌细胞吉西他滨化疗敏感性

殷雷1,殷睿2,李文佳3,刘帅1,吕家驹1   

  1. 1. 山东大学附属省立医院泌尿外科, 山东 济南 250021;2. 山东大学附属生殖医院医务科, 山东 济南 250001;3. 山东大学附属省立医院心内科, 山东 济南 250021
  • 收稿日期:2016-04-06 出版日期:2017-08-10 发布日期:2017-08-10
  • 通讯作者: 吕家驹. E-mail:kyoto2310@sina.com E-mail:kyoto2310@sina.com
  • 基金资助:
    山东省自然科学基金面上项目(2014ZRB14081);山东省自然科学基金(2014ZRB14513);山东省重点研发计划(2015GSF118055);山东省医药卫生科技发展计划(2014WS0341)

CYLD improves bladder cancer gemcitabine chemosensitivity via suppressing autophagy

YIN Lei1, YIN Rui2, LI Wenjia3, LIU Shuai1, L(¨overU)Jiaju1   

  1. 1. Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    2. Center for Reproductive Medicine Affiliated to Shandong University, Jinan 250001, Shandong, China;
    3. Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2016-04-06 Online:2017-08-10 Published:2017-08-10

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摘要： 目的 探讨肿瘤抑制因子CYLD提高膀胱癌细胞吉西他滨化疗敏感性。 方法 构建CYLD过表达质粒转染的人膀胱癌细胞株T24、253J,将细胞分为仅加入脂质体的对照组,转染空载质粒的空载组和CYLD组。Transwell实验检测CYLD对膀胱癌细胞迁移/侵袭能力的影响,CCK8法检测膀胱癌细胞对吉西他滨的化疗敏感性,Western blotting、吖啶橙染色、电镜等检测自噬蛋白表达水平。 结果 与对照组和空载组相比,CYLD组通过Transwell小室的细胞数目明显减少(P<0.05),24 h半抑制浓度(IC50)明显降低(P<0.05),自噬相关蛋白LC3、Beclin 1表达降低,p62表达增高,吖啶橙染色及电镜观察发现自噬溶酶体及自噬泡减少。 结论 肿瘤抑制因子CYLD可以抑制膀胱癌细胞的迁移/侵袭能力,并通过抑制自噬提高膀胱癌细胞对吉西他滨的化疗敏感性。

关键词: CYLD基因, 膀胱肿瘤, 吉西他滨, 自噬, 化疗敏感性

Abstract: Objective To explore the tumor suppressor CYLD in improving bladder cancer gemcitabine chemosensitivity. Methods The CYLD over-expressing plasmid was constructed and transfected into human bladder cancer cell lines T24 and 253J, then the cells were divided into control group treated with liposome, empty plasmid transfection group and CYLD group. The effect of CYLD on the migration/invasion ability of bladder cancer cells was measured by Transwell assays. The chemosensitivity to gemcitabine was tested by CCK-8 assay. Autophagy-related proteins were detected by Western blotting, acridine orange staining, and transmission electron microscopy. Results Compared with the control group and empty plasmid transfection group, CYLD group had significantly decreased cell numbers in Transwell chambers(P<0.05); significantly reduced 50% cell growth inhibition in 24 h(IC50)(P<0.05); decreased expressions of LC3 and Beclin 1, but elevated expression of p62; decreased autophagy lysosomes and autophagic vacuoles. Conclusion CYLD can decrease the ability of migration/invasion and improve gemcitabine chemosensitivity by sup- 山 东 大 学 学 报 (医 学 版)55卷8期 -殷雷,等.CYLD抑制自噬提高膀胱癌细胞吉西他滨化疗敏感性 \=-pressing autophagy in bladder cancer cells.

Key words: CYLD gene, Chemosensitivity, Autophagy, Bladder cancer, Gemcitabine

中图分类号: 

  • R574
[1] Zhang Y, Sun Y, Chen T, et al. Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population[J]. Int J Mol Sci, 2014, 15(11):19330-19341.
[2] Sun L, Lu J, Niu Z, et al. A Potent chemotherapeutic strategy with Eg5 inhibitor against gemcitabine resistant bladder cancer[J]. PLoS One, 2015, 10(12):e14484-14499.
[3] Ni F, Zhao H, Cui H, et al. MicroRNA-362-5p promotes tumor growth and metastasis by targeting CYLD in hepatocellular carcinoma[J]. Cancer Lett, 2015, 356(2 Pt B):809-818.
[4] Liu S, Lv J, Han L, et al. A pro-inflammatory role of deubiquitinating enzyme cylindromatosis(CYLD)in vascular smooth muscle cells[J]. Biochem Biophys Res Commun, 2012, 420(1):78-83.
[5] Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy(3rd edition)[J]. Autophagy, 2016, 12(1):1-222.
[6] Desantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014[J]. CA Cancer J Clin, 2014, 64(4):252-271.
[7] Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer:long-term results in 1,054 patients[J]. J Clin Oncol, 2001, 19(3):666-675.
[8] Bignell GR, Warren W, Seal S, et al. Identification of the familial cylindromatosis tumour-suppressor gene[J]. Nat Genet, 2000, 25(2):160-165.
[9] Sun B, Li L, Ma W, et al. MiR-130b inhibits proliferation and induces apoptosis of gastric cancer cells via CYLD[J]. Tumour Biol, 2016, 37(6):7981-7987.
[10] Yang JM, Xu Z, Wu H, et al. Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells[J]. Mol Cancer Res, 2003, 1(6):420-427.
[11] Hunstig F, Schulz S, Nieten I, et al. A case of Brooke-Spiegler syndrome with a novel mutation in the CYLD gene in a patient with aggressive non-Hodgkin's lymphoma[J]. J Cancer Res Clin Oncol, 2016, 142(4):845-848.
[12] Zhao Y, Ma CA, Wu L, et al. CYLD and the NEMO zinc finger regulate tumor necrosis factor signaling and early embryogenesis[J]. J Biol Chem, 2015, 290(36):22076-22084.
[13] 向波, 易梅, 李小玲, 等. 细胞自噬在肿瘤发生发展中的作用[J]. 生物化学与生物物理进展, 2012, 3:241-249. XIANG Bo, YI Mei, LI Xiaoling, et al. Progress on role of autophagy in cancer[J]. Progress in Biochemistry and Biophysics, 2012, 3:241-249.
[14] Ozpolat B, Benbrook DM. Targeting autophagy in cancer management-strategies and developments[J]. Cancer Manag Res, 2015, 7:291-299.
[15] Bauckman KA, Mysorekar IU. Ferritinophagy drives uropathogenic Escherichia coli persistence in bladder epithelial cells[J]. Autophagy, 2016, 12(5):850-863.
[16] Chen L, Ye HL, Zhang G, et al. Autophagy inhibition contributes to the synergistic interaction between EGCG and doxorubicin to kill the hepatoma Hep3B cells[J]. PLoS One, 2014, 9(1):e85771-85783.
[17] Liu S, Xie F, Wang H, et al. Ubenimex inhibits cell proliferation, migration and invasion in renal cell carcinoma:the effect is autophagy-associated[J]. Oncol Rep, 2015, 33(3):1372-1380.
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