Two hour exposure to sodium butyrate sensitizes bladder cancer to anticancer drugs.
OBJECTIVE
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.
Wang
Degui
D
Institute of Urology, Lanzhou University Second Hospital, and School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
Wang
Zhiping
Z
Tian
Binqiang
B
Li
Xiaoming
X
Li
Shigang
S
Tian
Yingxia
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002087:Butyrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D016685:Mitomycin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D002087:Butyrates; D016685:Mitomycin; D004317:Doxorubicin; D002945:Cisplatin