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抗がん剤の副作用と耐性化に着目したｃｙｃｌｏｏｘｙｇｅｎａｓｅ阻害薬の効果の検証

验证环氧合酶抑制剂的有效性，重点关注副作用和抗癌药物耐药性

基本信息

批准号：
19J11051
负责人：
岡本敬介
金额：
$ 1.34万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2019
资助国家：
日本
起止时间：
2019-04-25 至 2021-03-31
项目状态：
已结题

项目摘要

がん幹細胞に抗腫瘍効果を示すNSAIDsの探索: シスプラチンの殺細胞効果に影響を及ぼすNSAIDsが、がん細胞の種類によって効果が異なるかを明らかとするため、ヒト肺がん細胞株であるA549とSBC-3間における細胞生存率を比較した。その結果、検討に用いた17種類のNSAIDsにおいて、シスプラチン耐性前後ともに強い相関性が認められ、NSAIDsががん細胞に及ぼす効果はがん細胞の種類に依存しないことを見出した。NSAIDsによるシスプラチンの治療効果向上: これまでの検討により、シスプラチン起因性腎障害 (CIN) を増悪させずシスプラチンの抗腫瘍効果を高めるNSAIDsとしてジクロフェナクを、CINを軽減させつつがん幹細胞においてシスプラチンの抗腫瘍効果を高めるNSAIDsとしてセレコキシブを見出した。これらNSAIDsがシスプラチンの抗腫瘍効果と副作用に及ぼす影響を同時に検証するため、ヒト肺がん細胞株をヌードマウスに移植したXenograftモデルを構築し、抗腫瘍効果を評価した。シスプラチン単独投与では十分な抗腫瘍効果が認められなかった一方で、ジクロフェナク併用投与はシスプラチンの抗腫瘍効果を高めることが明らかとなった。また、セレコキシブ併用投与は軽微にシスプラチンの抗腫瘍効果を減弱させる傾向を示した。さらに、腎障害マーカーの1つであるKidney injury molecule 1 (Kim-1) を評価したところ、シスプラチン投与により発現が上昇したKim-1に対し、ジクロフェナクとセレコキシブは影響を及ぼさず、これらNSAIDsはCINを増強させないことが明らかとなった。以上の結果より、ジクロフェナクはシスプラチンの副作用であるCINを増強させずにシスプラチンの抗腫瘍効果を高めるNSAIDsであることを見出した。

The results showed that there was a significant difference in the survival rate of the cell line A549SBC-3, the cell line A549, the cell line A549SBC-3, the cell line A549SBC-3, the cell line A549SBC-3. The results show that there are significant differences in the performance of NSAIDs cells, NSAIDs cells, and so on. The result of the NSAIDs treatment was that the cause of the disease (CIN) was higher than that of the control group (CIN). The results of the treatment were higher than that of the control group (P < 0.01). The results showed that the disease was not caused by the cause of the disease (CIN). The results showed that the results of the treatment were higher than those of the control group, and the results showed that the results of the treatment were higher than those of the control group. In order to prevent the side effects, NSAIDs and lung cancer cell lines were grafted at the same time to prevent the side effects. At the same time, the cell lines of lung cancer and lung cancer were not transplanted into Xenograft cells. If you don't want to vote alone, you won't be able to do anything. You can't tell you what to do. Please tell me how to use it to show you that you are weak and weak. Please check that Kidney injury molecule 1 (Kim-1) has a bad effect on your computer, and that you can see that you have a Kim-1 problem, that you have a bad picture, that you have a bad picture, and that you have a good picture of NSAIDs. The results of the above results showed that the side effects of CIN were significantly higher than those of the control group (P < 0.01). The results of the above results showed that the side effects were significantly higher than those of the control group (P < 0.05). The results showed that the side effects of the above results were significantly higher than those of the control group (P < 0.05). The results showed that the side effects of the above results were significantly higher than those of the control group.