Antidiabetic adiponectin receptor agonist AdipoRon suppresses tumour growth of pancreatic cancer by inducing RIPK1/ERK-dependent necroptosis.
Antidiabetic adiponectin receptor agonist AdipoRon suppresses tumour growth of pancreatic cancer by inducing RIPK1/ERK-dependent necroptosis.
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DOI：
10.1038/s41419-018-0851-z
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发表时间：
2018-07-23
影响因子：
9
通讯作者：
Takenaga K
中科院分区：
文献类型：
--
作者：
Akimoto M;Maruyama R;Kawabata Y;Tajima Y;Takenaga K
低循环脂联素（APN）水平和胰腺癌的发展之间的关联已被报道。然而，APN对胰腺癌细胞的生长和存活的影响仍然是难以捉摸的。在这里，我们研究了抗糖尿病APN受体（AdipoR）激动剂AdipoRon和APN对人胰腺癌细胞的影响。我们发现AdipoRon而不是APN主要通过坏死性凋亡诱导MIAPaCa-2细胞死亡。从机制上讲，虽然AdipoRon和APN都以AdipoR依赖的方式激活AMPK和p38 MAPK，从而增强生存信号，但只有AdipoRon通过线粒体Ca 2+过载诱导快速线粒体功能障碍，然后通过RIPK 1和ERK 1/2激活产生超氧化物。AdipoRon口服给药抑制MIAPaCa-2肿瘤生长，无严重不良反应，并杀死从胰腺癌患者分离的癌细胞。因此，AdipoRon可能是一种治疗剂对胰腺癌以及糖尿病.
The association between lower circulating adiponectin (APN) levels and the development of pancreatic cancer has been reported. However, the effect of APN on the growth and survival of pancreatic cancer cells remains elusive. Here, we investigate the effects of the anti-diabetic APN receptor (AdipoR) agonist AdipoRon and APN on human pancreatic cancer cells. We found that AdipoRon, but not APN, induces MIAPaCa-2 cell death, mainly through necroptosis. Mechanistically, although both AdipoRon and APN activate AMPK and p38 MAPK in an AdipoR-dependent manner that elicits survival signals, only AdipoRon induces rapid mitochondrial dysfunction through mitochondrial Ca2+ overload, followed by superoxide production via RIPK1 and ERK1/2 activation. Oral administration of AdipoRon suppresses MIAPaCa-2 tumour growth without severe adverse effects and kills cancer cells isolated from patients with pancreatic cancer. Thus, AdipoRon could be a therapeutic agent against pancreatic cancer as well as diabetes.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
7.7
作者：
Andersen DK;Korc M;Petersen GM;Eibl G;Li D;Rickels MR;Chari ST;Abbruzzese JL
通讯作者：
Abbruzzese JL
DOI：
10.1016/0885-4505(92)90018-t
发表时间：
1992-04-01
期刊：
BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY
影响因子：
--
作者：
KLER, RS;SHERRATT, HSA;TURNBULL, DM
通讯作者：
TURNBULL, DM
影响因子：
10.3
作者：
Bao, Ying;Giovannucci, Edward L.;Wolpin, Brian M.
通讯作者：
Wolpin, Brian M.
影响因子：
82.9
作者：
Berg, AH;Combs, TP;Scherer, PE
通讯作者：
Scherer, PE