Sodium valproate enhances the cytotoxicity of immune cells to human bladder cancer cells
-
摘要: 目的:探讨丙戊酸钠(VPA)对膀胱癌细胞MICA表达的影响以及所产生的肿瘤免疫作用,以期为防治膀胱癌复发和浸润提供新的治疗方法。方法:采用不同浓度VPA处理人膀胱尿路上皮癌T24细胞后,用半定量RT-PCR和流式细胞术检测癌细胞中MICA mRNA和蛋白表达。用乳酸脱氢酶法检测外周血单个核细胞(PBMCs)对经VPA处理的T24细胞的杀伤作用。结果:VPA从mRNA和蛋白水平诱导T24细胞表达MICA,并增强T24细胞对PBMCs细胞毒作用的敏感性。结论:VPA能增强膀胱癌对免疫细胞杀伤作用的敏感性,可作为防治膀胱癌的辅助药物。Abstract: Objective:To investigate the effect of sodium valproate (VPA) on the expression of MICA and PBMCs-mediated cytotoxicity in T24 bladder cancer cells so as to provide a new method for treatment and prevention of recurrent and infiltrating bladder cancer.Method:T24 cancer cells were treated with VPA and the expression of MICA at the mRNA and protein levels were analyzed by RT-PCR and flow cytometry. Cytotoxicity of PBMCs against the T24 cells was investigated with the lactate dehydrogenase release assay. Result:VPA increased MICA expression in T24 cells and sensitizes cancer cells to cytotoxicity of PBMCs.Conclusion:VPA sensitizes human bladder cancer cells to cytotoxicity of immune cells.
-
Key words:
- bladder cancer /
- sodium valproate /
- NKG2D /
- MICA
-
-
[1] Higuchi T, Shimizu M, Owaki A, et al.A possible mechanism of intravesical BCG therapy for human bladder carcinoma:involvement of innate effector cells for the inhibition of tumor growth[J].Cancer Immunol Immunother, 2009, 58 (8):1245-1255.
[2] Duenas-Gonzalez A, Candelaria M, Perez-Plascencia C, et al.Valproic acid as epigenetic cancer drug:preclinical, clinical and transcriptional effects on solid tumors[J].Cancer Treat Rev, 2008, 34 (3):206-222.
[3] Nausch N, Cerwenka A.NKG2D ligands in tumor immunity[J].Oncogene, 2008, 27 (45):5944-5958.
[4] 卢善明, 邓汪东, 杨峰涛.膀胱尿路上皮癌中MHC I类链相关蛋白的表达及临床意义[J].汕头大学医学院学报, 2010, 23 (1):29-31.
[5] Barber A, Zhang T, DeMars L R.Chimeric NKG2D receptor-bearing T cells as immunotherapy for ovarian cancer[J].Cancer Res, 2007, 67 (10):5003-5008.
[6] Busche A, Goldmann T, Naumann U, et al.Natural killer cell-mediated rejection of experimental human lung cancer by genetic overexpression of major histocompatibility complex class I chain-related gene A[J].Hum Gene Ther, 2006, 17 (2):135-146.
[7] Carafa V, Miceli M, Altucci L, et al.Histone deacetylase inhibitors:apatent review (2009-2011)[J].Expert Opin Ther Pat, 2013, 23 (1):1-17.
[8] Khan A N, Tomasi T B.Histone deacetylase regulation of immune gene expression in tumor cells[J].Immunol Res, 2008, 40 (2):164-78.
[9] Byun S S, Kim F J, Khandrika L, et al.Differential effects of valproic acid on growth, proliferation and metastasis in HTB5 and HTB9 bladder cancer cell lines[J].Cancer Lett, 2009, 281 (2):196-202.
[10] Chen C L, Sung J, Cohen M, et al.Valproic acid inhibits invasiveness in bladder cancer but not in prostate cancer cells[J].J Pharmacol Exp Ther, 2006, 319 (2):533-542.
[11] Armeanu S, Bitzer M, Lauer U M.Natural killer cellmediated lysis of hepatoma cells via specific induction of NKG2D ligands by the histone deacetylase inhibitor sodium valproate[J].Cancer Research, 2005, 65 (14):6321-6329.
[12] Yang F, Shao Y, Yang F, et al.Valproic acid upregulates NKG2D ligand expression and enhances susceptibility of human renal carcinoma cells to NK cell-mediated cytotoxicity[J].Arch Med Sci, 2013, 9 (2):323-331.
[13] Yamanegi K, Yamane J, Kobayashi K, et al.Sodium valproate, a histone deacetylase inhibitor, augments the expression of cell-surface NKG2D ligands, MICA/B, without increasing their soluble forms to enhance susceptibility of human osteosarcoma cells to NK cellmediated cytotoxicity[J].Oncol Rep, 2010, 24 (6):1621-1627.
[14] Chávez-Blanco A, De la Cruz-Hernández E, Domínguez G I, et al.Upregulation of NKG2D ligands and enhanced natural killer cell cytotoxicity by hydralazine and valproate[J].Int J Oncol, 2011, 39 (6):1491-1499.
[15] Pfeiffer M M, Burow H, Schleicher S, et al.Influence of Histone Deacetylase Inhibitors and DNA-Methyltransferase Inhibitors on the NK Cell-Mediated Lysis of Pediatric B-Lineage Leukemia[J].Front Oncol, 2013, 3:99.
[16] Suzuki T, Terao S, Acharya B, et al.The antitumour effect of {gamma}{delta} T-cells is enhanced by valproic acid-induced up-regulation of NKG2D ligands[J].Anticancer Res, 2010, 30 (11):4509-4513.
-
计量
- 文章访问数: 107
- PDF下载数: 91
- 施引文献: 0