The usefulness of the combination of metformin with TACE based on hypoxia response characteristics of hepatocellular carcinoma
| Project/Area Number |
17K10430
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Hirosaki University |
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Principal Investigator |
Sato Mariko 弘前大学, 医学部附属病院, 助教 (30645263)
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| Co-Investigator(Kenkyū-buntansha) |
廣瀬 勝己 一般財団法人脳神経疾患研究所, 南東北BNCT研究センター, 診療所長 (60623767)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肝細胞癌 / 治療抵抗生 / 低酸素 / シスプラチン / メトホルミン / 肝動脈化学塞栓療法（TACE） / Metformin / CDDP / アポトーシス / TACE / HCC / ＴＡＣＥ / ＲＯＳ / 癌幹細胞 |
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| Outline of Final Research Achievements |
We investigated the impact of hypoxia on cytotoxic effect of cisplatin (CDDP) using apoptosis analysis. In hypoxic (1% O2) cells, the resistance to CDDP was observed. And, the combination of CDDP and 1 mM metformin increased the apoptotic cells compared to treatment with CDDP alone in hypoxic cells. However, CDDP combined with metformin did not affect apoptosis in normoxic cells.
In this study, we have shown that a low concentration of metformin attenuates hypoxia-induced resistance to CDDP in liver cancer HepG2 cells. Thus, low-dose metformin has high potential to enhance the therapeutic effect of CDDP in hepatoblastoma and to improve the prognosis of patients.
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| Academic Significance and Societal Importance of the Research Achievements |
肝細胞癌に対する肝動脈化学塞栓療法 (TACE)は肝機能や肝内血管開存性を温存できるという利点を有し、生存率を有意に延長するが、再発は8割にも昇る。TACEによる抗腫瘍効果を高める目的で、腫瘍増殖抑制作用や化学療法および放射線治療の増感作用が報告されているメトホルミンに着目した。
肝癌細胞株HepG2を用いたアポトーシス解析の結果、低酸素（1% O2）細胞ではシスプラチン抵抗性が認められたが、低容量メトホルミンをシスプラチンに併用することで、低酸素細胞におけるシスプラチンの抗腫瘍効果を増強することが明らかとなった。低容量メトホルミンがTACEの局所効果向上 につながる可能性がある。
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Report
(4 results)
Research Products
(1 results)
