Ultrastructural change due to acquired cisplatin resistance in human bladder cancer cells

Abstract

Cis-diaminedichloroplatinum (cisplatin) has therapeutic efficacy against advanced bladder cancer. However, the response is often limited due to appearance of drug-resistant tumor cells. Recently, we established a cisplatin-resistant human bladder cancer cell line, T24/R2, from T24 human bladder cancer cell line, which shows 18-fold resistance to cisplatin by the stepwise exposure of increasing concentrations of cisplatin. A light microscopic (LM) and transmission electron microscopic (EM) examination was performed to investigate the morphological and ultrastructural changes during induction of drug resistance. In LM, the cytoplasm of T24R2 cells showed plumper pattern than that of T24 parent cells. In EM, the chromatin pattern of T24R2 cells was finely dispersed compared to T24 cells, which were coarse and aggregated. The mitochondrial volume, rough endoplasmic reticulum, polyribosomes and ribosomes were moderately increased in T24R2 cells. The cell membrane showed ruffled border and great amount of double membrane vesicles and pinocytic vesicles were observed in the cell surface of T24R2 cells, which were seldom observed in T24 cells. With these findings, we concluded that human bladder cancer cells underwent morphological and ultrastructural changes during acquiring of resistance to cisplatin. We could suggest that these changes might be involved in the drug resistance mechanism in human bladder cancer cells.