| RRC ID |
72614
|
| 著者 |
Haraguchi-Suzuki K, Kawabata-Iwakawa R, Suzuki T, Suto T, Takazawa T, Saito S.
|
| タイトル |
Local anesthetic lidocaine-inducible gene, growth differentiation factor-15 suppresses the growth of cancer cell lines.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Administration of local anesthetics, such as lidocaine, in the perioperative period improves outcomes of cancer patients. However, its precise mechanism is still unresolved. The growth of human cancer cell lines, including HeLa cells, are suppressed by lidocaine treatment. We identified that growth differentiation factor-15 (GDF-15) was commonly upregulated in lidocaine-treated cancer cell lines. GDF-15 is a divergent member of the transforming growth factor-β (TGF-β) superfamily and it is produced as an unprocessed pro-protein form and then cleaved to generate a mature form. 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.
|
| 巻・号 |
12(1)
|
| ページ |
14520
|
| 公開日 |
2022-8-25
|
| DOI |
10.1038/s41598-022-18572-3
|
| PII |
10.1038/s41598-022-18572-3
|
| PMID |
36008442
|
| PMC |
PMC9411556
|
| MeSH |
Anesthetics, Local / pharmacology
Growth Differentiation Factor 15* / genetics
Growth Differentiation Factor 9
HeLa Cells
Humans
Lidocaine / pharmacology
Neoplasms*
Transforming Growth Factor beta / metabolism
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007)
Hep G2(RCB1648) |
