口腔がん細胞のシスプラチン耐性化に伴う白金系抗がん剤及び強心配糖体に対する感受性の変化

Na,K-ATPase

北海道歯学会

北海道歯学雑誌

Purpose: Cancer chemotherapy using platinum-based anticancer agents is inhibited by cancer cell cisplatin resistance, but the mechanism is unknown. Hence, we examined how cisplatin-resi stant oral cancer cells changed their sensitivity toplatinum coordination complex and cardiac glycosides. Materials and methods: We used oral cancer cells (parent cell line: H1, KB) and cisplatin-resistant lines (resistant cell line: H1R, KBR). The cells were dispersed in a 96-wells plate and inc ubated with 8, 16, 31, 63, 125, 250, and 500 μM cisplatin, carboplatin, or nedaplatin (anticancer agent) for 6, 12, 24, 48, and 72 h in the absence or presence of ouabain. The survival rate of the cells was measured by intracellular adenosine triphosphate content using ViaLigh plus kit (LONZA). Results and discussion: 1. In all experimental conditions, H1 and KB, H1R, and KBR showed similar results as parent or resistant cell lines. 2. The viable cell count of a parent or resistant cells decreased in a concentration and time-dependent manner in response to the anticancer agent. 3. When compared to the parent cell line, the resistant cell line showed resistance to not only cisplatin but also carboplatin and nedaplatin. 4. In parent and resistant cell lines, the 50% inhibitory concentrations of the anticancer agent ranged from low to high in the order of cisplatin, nedaplatin, and carboplatin. 5. In the presence of a low concentration anticancer agent, the number of parent cells was reduced, but it was protected at higher concentrations. On the other hand, there was no such concentration range for anticancer agent-resistant cell lines. 6. The viable cell count of a parent or resistant cells decreas ed in a concentration and time-dependent manner in response to ouabain. 7. In presence of ouabain, there was a concentration range of anticancer agents that protected against a decrease in the number of cells. This effect occurred only in the parent cell l ine incubated with cisplatin, but not in the parent or resistant cell line incubated with carboplatin or nedaplatin. Conclusion: Cisplatin resistance in the oral cancer cell lines H1 and KB showed cross-resistance to carboplatin and nedaplatin. The effect of the platinum coordination complex and cardiac glycosides changed as they became cisplatin-resistant.