Local anesthetic lidocaine-inducible gene, growth differentiation factor-15 suppresses the growth of cancer cell lines.
Local anesthetic lidocaine-inducible gene, growth differentiation factor-15 suppresses the growth of cancer cell lines.
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DOI：
10.1038/s41598-022-18572-3
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发表时间：
2022-08-25
影响因子：
4.6
通讯作者：
Saito, Shigeru
中科院分区：
文献类型：
--
作者：
Haraguchi-Suzuki, Keiko;Kawabata-Iwakawa, Reika;Suzuki, Toru;Suto, Takashi;Takazawa, Tomonori;Saito, Shigeru
在围手术期使用局部麻醉剂（例如利多卡因）可以改善癌症患者的预后。然而，其确切机制仍未解决。利多卡因治疗可抑制人类癌细胞系（包括 HeLa 细胞）的生长。我们发现，在利多卡因处理的癌细胞系中，生长分化因子 15 (GDF-15) 通常上调。 GDF-15 是转化生长因子-β (TGF-β) 超家族的一个不同成员，它以未加工的前蛋白形式产生，然后裂解生成成熟形式。在利多卡因处理的 HeLa 细胞中，观察到内质网 (ER) 中 GDF-15 的产量增加，并且未加工的 GDF-15 前蛋白形式被分泌到细胞外。此外，利多卡因诱导细胞凋亡，并且细胞凋亡诱导型 Tribbles 同源物 3 (TRIB3) 在利多卡因处理的癌细胞系中也普遍上调。此外，利多卡因还诱导了转录因子C/EBP同源蛋白（CHOP），它不仅是GDF-15的正调节因子，而且是TRIB3的正调节因子。小干扰 RNA (siRNA) 敲低 GDF-15 或 TRIB3 表达可抑制利多卡因诱导的生长抑制和细胞凋亡。这些观察结果表明，利多卡因通过增加 GDF-15 和 TRIB3 的表达来抑制癌细胞的生长，表明其作为癌症治疗的潜在应用。
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.
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影响因子：
2.3
作者：
Bauskin, Asne R.;Jiang, Lele;Breit, Samuel N.
通讯作者：
Breit, Samuel N.
影响因子：
5.2
作者：
Hong Y;Lee J;Moon H;Ryu CH;Seok J;Jung YS;Ryu J;Baek SJ
通讯作者：
Baek SJ
影响因子：
64.5
作者：
Cubillos-Ruiz JR;Bettigole SE;Glimcher LH
通讯作者：
Glimcher LH
影响因子：
2.8
作者：
Lang, Alon;Ben Horin, Shomron;Chowers, Yehuda
通讯作者：
Chowers, Yehuda
DOI：
10.1158/1078-0432.ccr-13-1106
发表时间：
2013-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Liu R;Li X;Gao W;Zhou Y;Wey S;Mitra SK;Krasnoperov V;Dong D;Liu S;Li D;Zhu G;Louie S;Conti PS;Li Z;Lee AS;Gill PS
通讯作者：
Gill PS