[Mechanism of intravesical instillation of pirarubicin for preventing recurrence of non-muscle invasive bladder cancer].
OBJECTIVE
To evaluate the apoptosis-inducing effect of intravesical instillation of pirarubicin (THP) on bladder cancer and normal bladder tissue, and explore the mechanism of such treatment for preventing recurrence of non-muscle invasive bladder cancer.


METHODS
Forty patients with primary non-muscle invasive bladder cancer were treated in our hospital from January 2006 to October 2008. The patients were divided into three groups, including 15 cases treated by intravesical instillation of THP (30 mg/50 ml, 0.5 hours) at 1 hour, 15 cases at 24 hours before transuretheral resection of bladder tumor (TUR-BT), and 10 cases in control group who received TUR-BT only. The THP uptake of the tumor and normal bladder tissues was observed by fluorescence microscopy, the apoptosis was assessed with TUNEL staining, and immunohistochemistry was used to detect the expression of bcl-2 and bax.


RESULTS
Seldom fluorescence of THP in normal bladder tissues and some diffuse fluorescence reaching the muscular layer in the tumor area were observed after THP instillation at 1 hour before TUR-BT. The fluorescence of THP could still be observed in the tumor tissues at 24 hours after THP instillation. The apoptosis indexes (AI) of tumors in the chemotherapy groups were significantly higher than that in the control group (P < 0.01). There was a correlation between bcl-2/bax ratio and AI.


CONCLUSIONS
Pirarubicin can be uptaken by bladder cancer tissue selectively and induces apoptosis of tumor cells. The changes of expression of bcl-2 and bax and decreasing of the bcl-2/bax ratio may be an important mechanism of action of the intravesical instillation of THP for preventing recurrence of non-muscle invasive bladder cancer.
Li
Qing
Q
Department of Urology, Peking University People's Hospital, Beijing 100044, China.
Xu
Tao
T
Wang
Xiao-feng
XF
D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015653:Cystectomy; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011300:Preoperative Care; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin; C027260:pirarubicin