Ca2+ Mobilization of CDDP-Resistant KB Cells.

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Cisplatin (CDDP) is one of the most potent and useful anticancer agents for head & neck cancers. The cytotoxicity of this drug is known to include inhibition of DNA synthesis. However, the development of resistance by tumor cells to this drug is an important problem. In order to elucidate the mechanism of CDDP resistance, we established CDDPresistant KB cell lines (KBrc cells) from oral epidermal carcinoma cell lines (KB cells). In this study, we investigated the mobilization of intracellular free calcium ion concentration ([Ca2+]i) to elucidate the mechanism of CDDP resistance in case of contact with a high dose of CDDP (500μg/ml) using these cell lines. Incubation with CDDP markedly increased [Ca2+]i in both cell lines. In contrast, a low dose of CDDP resulted in the reduction of [Ca2+]i toward the resting level. Furthermore, the peak and plateau of [Ca2+]i were higher in KB cells than in KBrc cells, and the speed toward the plateau phase was later in KB cells in comparison with that in KBrc cells. This increase in [Ca2+]i was thought to be due mainly to an influx of extracellular calcium ions. Moreover, the viability of KB cells was lower than that of KBrc cells. It was speculated that KBrc cells possesed the ability to protect CDDP compared with KB cells and the change of [Ca2+]i in KBrc cells was less than that in KB cells. It appears that CDDP can injure cell membranes as well as inhibit DNA synthesis.
耳鼻咽喉科臨床学会の論文