| Project/Area Number |
19K24005
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0905:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Gunma University |
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Principal Investigator |
Suzuki Keiko 群馬大学, 医学部附属病院, 助教 (50846897)
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| Project Period (FY) |
2019-08-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 局所麻酔薬 / 癌細胞株増殖抑制 / GDF-15 / TRIB3 / Ki-67 / 癌細胞増殖抑制 / リドカイン / 小胞体ストレス / 腫瘍細胞 / 腫瘍免疫 / 徐放化局所麻酔薬 / 腫瘍増殖能 |
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| Outline of Research at the Start |
吸入麻酔薬や静脈麻酔薬、オピオイドや局所麻酔薬などの麻酔薬が細胞の増殖能や免疫能を修飾し生命予後に影響を与えることが多く報告されている。特に、術後鎮痛として重要な硬膜外麻酔や末梢神経ブロックなどの区域麻酔に使用される局所麻酔薬が細胞増殖や免疫系に影響を与え、癌において良好な予後が示唆されているが、そのメカニズムは充分に解明されていない。そのため、本研究は癌細胞において、局所麻酔薬により発現が変化する遺伝子の探索を行い、局所麻酔薬が癌細胞の増殖能に与える影響、ならびに局所麻酔薬が癌において免疫機能をどのように修飾するかを解析する。
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| Outline of Final Research Achievements |
We identified that growth differentiation factor-15 (GDF-15) was commonly upregulated and Ki-67 was downregulated in lidocaine-treated cancer cell lines. In lidocaine-treated HeLa cells, increased production of GDF-15 in the endoplasmic reticulum (ER) was observed and unprocessed pro-protein form of GDF-15 was secreted extracellularly. Further, lidocaine induced apoptosis and apoptosis-inducible Tribbles homologue 3 (TRIB3) was also commonly upregulated in lidocaine-treated cancer cell lines. In addition, transcription factor C/EBP homologous protein (CHOP), which is a positive regulator of not only GDF-15 but TRIB3 was also induced by lidocaine. Lidocaine-induced growth suppression and apoptosis was suppressed by knockdown of GDF-15 or TRIB3 expression by small interference RNA (siRNA). These observations suggest that lidocaine suppresses the growth of cancer cells through increasing GDF-15 and TRIB3 expression, suggesting its potential application as cancer therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により局所麻酔薬が抗腫瘍効果を有する可能性が示唆された。
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