Bone Abstracts

Backgrounds: Bladder cancer is the most common malignancy and also highest mortality of the urinary tract cancer. Urothelial cell carcinoma (UCC) is the most histopathological subtype of bladder cancer. Epidemiological studies have indicated that bladder cancer risk for cigarette smoking is more than twice than never smoking and that current cigarette smoking triples bladder cancer risk relative to never smoking. Cigarette smoking after bladder cancer diagnosis decreases cancer therapeutic response and increases second cancer risk among cancer survivors. Since the urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination, the toxic metabolites of cigarette smoking may store in urinary bladder for a longer period which increases the possibility of cell transformation of urothelial cells or UCC cells and therefore increases the risk in calcified of bladder carcinogenesis or bladder cancer progression. Administration of cigarette smoking condensate (CSC) may be useful to realize overall inductive mechanisms of cigarette smoking during calcified of bladder carcinogenesis progression. Otherwise, voltage-gated Ca²⁺ channels were thought to be a main path for Ca²⁺ entry, also it became clear that a variety of other Ca²⁺-conducting channels may extremely effects in calcified bladder function.

Materials & methods: Calcified of human UCC cell line T24 and the immortalized normal proximal tubule epithelial cell line SV-HUC-1 were employed for analyzing biological effects and molecular regulation of CSC. T24 and SV-HUC-1 are continuously exposed to 0.1, 1, 4 μg/ml (0.1% CSC), and 10 μg/ml CSC in 0.1% DMSO for more than six months. In biological effects, CSC inductive effect on cell viability was evaluated by MTT assay and non-adhersive assay. And CSC inductive effects on cell migration and invasion were evaluated using wound-healing assay, boyden chamber transwell assay, and Matrigel-coated transwell assays. In molecular regulation, CSC modified miRNA expression profile was evaluated by quantitative real-time RT-PCR. For calcium influx factor (CIF), we investigate the gene, STIM1 which could effects calcified bladder cancer cell via CSC long term treatment.

Results: This study is designed to realize the CSC effects on microRNA regulation in calcified bladder carcinogenesis and progression. We found short-term (48 h) and long-term (6 months) treatment of CSC both increased cell viability and mobility of SV-HUC-1 normal urothelial cell line and T24 calcified of UCC cell lines. Besides, CSC treatment also modified documented UCC diagnostic miRNAs in SV-HUC-1 and modified documented prognostic miRNAs in T24.

In conclusion, we found CSC indeed promoted calcified of UCC carcinogenesis and progression via modifying miRNA expression.

Key Words: bladder cancer (urothelial cell carcinoma), cigarette smoking condensate, siRNA.