Two hour exposure to sodium butyrate sensitizes bladder cancer to anticancer drugs

被引:60
作者
Wang, Degui [1 ,2 ]
Wang, Zhiping [1 ]
Tian, Binqiang [1 ]
Li, Xiaoming [1 ]
Li, Shigang [2 ]
Tian, Yingxia [1 ]
机构
[1] Lanzhou Univ, Hosp 2, Inst Urol, Lanzhou 730030, Gansu, Peoples R China
[2] Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730030, Gansu, Peoples R China
关键词
bladder cancer; chemotherapy; combination; sodium butyrate;
D O I
10.1111/j.1442-2042.2008.02025.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Objectives: To investigate the inhibitory effect of sodium butyrate (NaB) on the proliferation of human bladder cancer cell lines and its synergetic effect with anticancer drugs in treating bladder cancer in vitro and in vivo. Methods: The inhibitory effects of NaB on human bladder cancer cell lines in vitro and the synergetic effect of NaB with mitomycin c, cisplatin (CDDP) and adriamycin were detected by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Hoechst staining and electron microscopy were used to observe morphology for apoptotic cells after NaB treatment. Fas, bcl-2 and caspase-3 were determined with flow cytometry. In vivo synergetic effects were detected in N-methyl-N-nitrosourea induced bladder cancer model rats. Results: NaB significantly inhibited the growth of bladder cancer cell lines in a concentration and time dependent manner. Better results of tumor inhibition have been achieved when NaB was combined with CDDP, mitomycin c and adriamycin, rather than used alone. Furthermore, 2 h exposure to NaB can sensitize bladder cancer to chemotherapy agents. The Bcl-2 expression in bladder cancer cells is decreased and caspase-3 expression increased after NaB treatment. Intravesical application of NaB combined with CDDP can significantly inhibit tumor growth and progression. Conclusions: NaB has a direct anticancer effect and can markedly enhance the action of several chemotherapy agents. 2 h expose to NaB can also sensitize bladder cancer to anticancer drugs. NaB may be an excellent candidate agent for intravesical application in treating bladder cancer.
引用
收藏
页码:435 / 441
页数:7
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