TRAIL and triptolide: an effective combination that induces apoptosis in pancreatic cancer cells.

TRAIL and triptolide: an effective combination that induces apoptosis in pancreatic cancer cells.
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TRAIL 和雷公藤甲素:诱导胰腺癌细胞凋亡的有效组合。

DOI:
10.1007/s11605-009-1065-6
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发表时间:
2010-02
影响因子:
3.2
通讯作者:
Vickers, Selwyn M.
Vickers, Selwyn M.
中科院分区:
医学3区
文献类型:
--
作者:
Borja-Cacho, Daniel;Yokoyama, Yumi;Chugh, Rohit K.;Mujumdar, Nameeta R.;Dudeja, Vikas;Clawson, Kimberly A.;Dawra, Rajinder K.;Saluja, Ashok K.;Vickers, Selwyn M.

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肿瘤学中的新兴疗法是通过抗死亡受体疗法诱导凋亡性细胞死亡。然而,胰腺癌对细胞凋亡具有抗性,包括抗死亡受体治疗。我们先前已经描述了雷公藤内酯醇如何在体外和体内降低胰腺癌细胞对凋亡的抵抗。我们假设雷公藤内酯醇降低胰腺癌细胞对肿瘤坏死因子相关凋亡诱导配体(TRAIL)的耐药性。本研究的目的是评估TRAIL和雷公藤甲素联合治疗对不同凋亡参数的影响。将四种不同的胰腺癌细胞系暴露于雷公藤内酯醇、TRAIL或两种药物的组合。我们评估了TRAIL和雷公藤内酯醇联合治疗对细胞活力、凋亡、caspase-3和caspase-9活性以及聚(ADP)-核糖聚合酶裂解的影响。胰腺癌细胞对TRAIL治疗具有抗性;然而,雷公藤内酯醇和TRAIL的联合治疗显著降低了所有细胞系中的细胞活力,并增加了caspase-3和caspase-9激活导致的凋亡性细胞死亡。胰腺癌对抗死亡受体治疗具有高度抗性,但TRAIL和雷公藤内酯醇的联合治疗是诱导胰腺癌细胞凋亡的有效治疗。
An emerging therapy in oncology is the induction of apoptotic cell death through anti-death receptor therapy. However, pancreatic cancer is resistant to apoptosis including anti-death receptor therapy. We have previously described how triptolide decreases resistance to apoptosis in pancreatic cancer cells in vitro and in vivo. We hypothesized that triptolide decreases tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in pancreatic cancer cells. The aim of this study was to evaluate the effects that combined therapy with TRAIL and triptolide have on different parameters of apoptosis. Four different pancreatic cancer cell lines were exposed to triptolide, TRAIL, or a combination of both drugs. We assessed the effects that combined therapy with TRAIL and triptolide has on cell viability, apoptosis, caspase-3 and caspase-9 activities, and poly(ADP)-ribose polymerase cleavage. Pancreatic cancer cells were resistant to TRAIL therapy; however, combined therapy with triptolide and TRAIL significantly decreased the cell viability in all the cell lines and increased apoptotic cell death as a result of caspase-3 and caspase-9 activation. Pancreatic cancer is highly resistant to anti-death receptor therapy, but combined therapy with TRAIL and triptolide is an effective therapy that induces apoptotic cell death in pancreatic cancer cells.
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