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Hokkaido University Collection of Scholarly and Academic Papers >
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北海道歯学雑誌 >
第43巻 >
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
| Title: | 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 |
| Other Titles: | Sensitivity changes to platinum coordination complex and cardiac
glycosides in cisplatin-resistant oral cancer cells |
| Authors: | 義達, 理恵子1 Browse this author | | 鈴木, 邦明2 Browse this author →KAKEN DB | | 吉村, 善隆3 Browse this author →KAKEN DB | | 南川, 元4 Browse this author →KAKEN DB | | 鄭, 漢忠5 Browse this author →KAKEN DB |
| Authors(alt): | Yoshitatsu, Rieko1 | | Suzuki, Kuniaki2 | | Yoshimura, Yoshitaka3 | | Minamikawa, Hajime4 | | Tei, Kanchu5 |
| Keywords: | 口腔がん細胞 | | シスプラチン耐性 | | 白金系抗がん剤 | | Na,K-ATPase | | ウアバイン | | oral cancer cells | | cisplatin resistance | | platinum coordination complex | | ouabain |
| Issue Date: | 15-Sep-2022 |
| Publisher: | 北海道歯学会 |
| Journal Title: | 北海道歯学雑誌 |
| Volume: | 43 |
| Start Page: | 19 |
| End Page: | 28 |
| Abstract: | 【目的】白金系抗がん剤による化学療法において耐性化が障害となるが，その機序には不明な点も多い．そこで耐性化の機構の検討を目的に，シスプラチン耐性化に伴う白金系抗がん剤及び抗がん活性を示す強心配糖体のウアバインに対する感受性の変化を検討した．
【材料と方法】口腔がん細胞株（親株：H1, KB）及びそれらのシスプラチン耐性株（耐性株：H1R, KBR）のシスプラチン，カルボプラチン及びネダプラチン（抗がん剤と総称）とウアバインに対する感受性の変化を検討した．細胞生存率を測定するために細胞内ATP量を測定した．
【結果と考察】1．H1とKB，H1RとKBRはそれぞれ親株と耐性株として類似した結果を示した．2．親株，耐性株とも抗がん剤の濃度及び作用時間に依存して細胞数は減少した．3．耐性株は，低濃度の抗がん剤に対して親株と比較して耐性を示した．4．親株，耐性株とも50％細胞数を減少するのに必要な抗がん剤の濃度はシスプラチン，ネダプラチン，カルボプラチンの順に増加した．5．親株は低濃度の抗がん剤存在下で細胞数が減少したが，さらに濃度が上がると細胞数の減少が抑制される濃度域が存在した．一方，耐性株は抗がん剤の濃度依存性に細胞数が減少するのみであった．6．親株及び耐性株はウアバインの濃度及び作用時間に依存して細胞数が減少した．7．適当な濃度の抗がん剤はウアバイン存在下での細胞数の減少を保護した．以上の結果は，口腔がん細胞及びそのシスプラチン耐性株に対する白金系抗がん剤の作用はその濃度によって異なることと，シスプラチン耐性化に伴いウアバインの作用も変化することを示唆する．
【結論】口腔がん細胞株であるH1及びKBのシスプラチン耐性化によりカルボプラチン及びネダプラチンに対する交叉耐性を示す．また，耐性化に伴い，白金系抗がん剤及び強心配糖体の作用が変化する． | | 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/86832 |
| Appears in Collections: | 北海道歯学雑誌 > 第43巻
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