Human urothelial carcinoma cell response to Sunitinib malate therapy in vitro

详细信息    查看全文

• 作者：Jin Wen ; Han-Zhong Li ; Zhi-Gang Ji ; Jing Jin
• 关键词：Sunitinib ; Sorafenib ; Cisplatin ; Bladder cancer ; Proliferation
• 刊名：Cancer Cell International
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：1
• 全文大小：1,424 KB
• 参考文献：1. Rock, EP, Goodman, V, Jiang, JX, Mahjoob, K, Verbois, SL, Morse, D (2007) Food and Drug Administration drug approval summary: sunitinib malate for the treatment of gastrointestinal stromal tumor and advanced renal cell carcinoma. Oncologist 12: pp. 107-13 CrossRef
  2. Roskoski, R (2007) Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun 356: pp. 323-8 CrossRef
  3. Motzer, RJ, Rini, BI, Bukowski, RM, Curti, BD, George, DJ, Hudes, GR (2006) Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295: pp. 2516-24 CrossRef
  4. Saltz, LB, Rosen, LS, Marshall, JL, Belt, RJ, Hurwits, HI, Eckhardt, SG (2007) Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. J Clin Oncol 25: pp. 4793-9 CrossRef
  5. Socinski, MA, Novello, S, Brahmer, JR, Rosell, R, Sanchez, JM, Belani, CP (2008) Multicenter, phase II trial of sunitinib in previously treated, advanced non-small-cell lung cancer. J Clin Oncol 26: pp. 650-6 CrossRef
  6. Yoon, CY, Lee, JS, Kim, BS, Jeong, SJ, Hong, SK, Byun, SS (2011) Sunitinib malate synergistically potentiates anti-tumor effect of gemcitabine in human bladder cancer cells. Korean J Urol 52: pp. 55-63 CrossRef
  7. Silay, MS, Miroglu, C (2007) Sunitinib malate and sorafenib may be beneficial at the treatment of advanced bladder cancer due to their antiangiogenic effects. Hypotheses 69: pp. 892-5 CrossRef
  8. Droller, MJ (1998) Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. J Urol 160: pp. 1932 CrossRef
  9. Chabannes, E, Bernardini, S, Wallerand, H, Bittard, H (2001) Angiogenesis in bladder: prognosis indicator and therapeutic target. Prog Urol 11: pp. 417-27
  10. Szarvas, T, J?ger, T, Droste, F, Becker, M, Kovalszky, I, Romics, I (2009) Serum levels of angiogenic factors and their prognostic relevance in bladder cancer. Pathol Oncol Res 15: pp. 193-201 CrossRef
  11. Liu, L, Zhu, D, Gao, R, Guo, H (2008) Expression of vascular endothelial growth factor, receptor KDR, and p53 protein in transitional cell carcinoma of the bladder. Urol Int 81: pp. 72-6 CrossRef
  12. Burstein, HJ, Elias, AD, Rugo, HS, Cobleigh, MA, Wolff, AC, Eisenberg, PD (2008) Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 26: pp. 1810-6 CrossRef
  
• 刊物主题：Cancer Research; Cell Biology;
• 出版者：BioMed Central
• ISSN：1475-2867

文摘

Objectives Bladder transitional cell carcinoma (TCC) is one of the most common solid malignancies in China. This study examined the antitumor effect and underlying mechanism of action of sunitinib malate in human bladder TCC in vitro. Methods Bladder TCC cell lines 5637 and BIU87 were maintained in 1640 medium and T24 cell lines in DMEM/F12 medium. All 3 cell lines were then exposed to graded concentrations (0.625-20?μmol/L) of sunitinib malate, sorafenib and cisplatin for 24-6 hours to determine the sensitivities to each drug. Cell viability was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] assay, and apoptosis was analyzed by flow cytometry. Cell apoptotic morphology was observed by a fluorescence microscope after DAPI (4-6-diamidino-2-phenylindole) staining. Protein concentrations were measured by western blot. Results Sunitinib malate showed a concentration-dependent inhibitory effect on the 5637, T24 and BIU87 cell lines with IC50’s of 1.74?μmol/L, 4.22?μmol/L, and 3.65?μmol/L, respectively. Cisplatin also exhibited good antitumor activity, but whereas sorafenib suppressed proliferation of the cells at concentrations of 10?μmol/L or higher, there was practically no response at lower concentrations. Sunitinib malate treatment resulted in an accumulation of cells in the sub-G1 phase, especially with the T24 and BIU87 cell lines, which induced apoptosis of the cells. Conclusions Sunitinib malate exerted marked inhibitory activity against bladder cancer cells. The cell growth inhibitory effect of the drug was related to induction of apoptosis. These results suggest that clinical application of sunitinib-based therapy for advanced bladder cancer is possible.