新規に開発したプラチナ製剤にカフェインを併用した化学療法を骨肉腫細胞株に対して施行し，シスプラチン同様に抗腫瘍効果の増強を確認できた．また新規プラチナ製剤はDNA2本鎖断裂を引き起こすことを確認し，シスプラチン同様の作用機序が示唆された．一方でシスプラチン耐性株に対しても交叉耐性を示さなかったことからシスプラチン耐性といった臨床上の大きな問題にも対応できる可能性が示唆された．
Each compound strongly caused concentration-dependent cytocidal effect. IC50 value of trinuclear compound is superior to cisplatin, and both complexes showed caffeine potentiation. Two novel platinum do not show cross resistance to cisplatin. Apoptosis induction and acetylation of histon H2AX were observed. In vivo, 1Pt showed almost same, 3Pt showed stronger antitumor effect compared to cisplatin.Two novel platinum complexes that we developed showed strong ant-tumor effect in osteosarcoma in vitro and in vivo. 3Pt shows superior anti-tumor effect compared to cisplatin. 1Pt shows strong in vivo anti-tumor activity. Apoptosis is induced by DNA double strand break. Novel platinum compounds may overcome cisplatin resistance.
骨肉腫に対する新規合成プラチナ錯体にカフェインを併用した化学療法の基礎的研究
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ME-PR-YAMAMOTO-N-kaken 2015-4p.pdf
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