Login to Access Video or Poster Abstract: MP48-12
Sources of Funding: none

Introduction

The second line chemotherapy against advanced bladder cancer has not been established. We hypothesize that highly activated genes after anti-cancer drug treatment is related to the key for predicting the anti-tumor effect . For this purpose, a comprehensive analysis using cDNA microarray was performed to identify the common target genes after treatment of chemotherapeutic agent.

Methods

Bladder cancer cell lines of T24, RT4, UMUC3, and prostate cancer cell line of PC3 were used as control. Clinical samples from 26 cases with muscle invasive bladder cancer who underwent radical cystectomy were also used. Anti-cancer drugs used were docetaxel (DTX), gemcitabine (GEM) and Cis-platinum (CDDP). The cell viability was evaluated by an MTT assay. Gene expression profiles in T24 cells were identified using cDNA microarray, which showed significant difference before and after treamnent of 1.1mM docetaxel (DTX). Individual gene expression was validated by quantitative RT-PCR. Functional study of the candidate genes was performed using specific siRNA transfection.

Results

We identified SERPINB2 gene with the GO term of “negative regulation of apoptosis� as extraordinarily activated gene after DTX treatment (Z score=7.509) . In T24 and UMUC3 cells, SERPINB2 expression was significantly increased in a stepwise manner of DTX concentration, while no significant elevation of SERPINB2 was found in RT4 cells (Table). Likewise, CDDP extraordinarily enhanced the SERPINB2 expression in T24 and UMUC3 , but not in RT4. On other hand, GEM significantly accelerated the SERPINB2 expression in T24, while it did not in UMUC3 and RT4. UMUC3 cells, in which high SERPINB2 expression was found before treatment, showed significant reduction of cell viability after transfection of SERPINB2 siRNA, suggesting that SERPINB2 might function as oncogene. In addition, in PC3 where SERPINB2 was highly expressed before treatment, SERPINB2 knockdown by siRNA transfection showed significant reduction of cancer cell survival. In clinical samples, there was no significant difference in SERPINB2 expression between normal and cancer tissues. Interestingly, SERPINB2 expression was significantly higher in 4 cases who underwent both neoadjuvant chemotherapy (NAC) and cystectomy than in 22 cases who did cystectomy alone.

Conclusions

In certain bladder cancers, SERPINB2 might function as oncogene and is highly up-regulated. Activation of SERPINB2, which is frequently found after anti-cancer agent treatment, might provide the essential information regarding the chemotherapeutic strategy in bladder cancer.

Funding

none