Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.
Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.
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DOI：
10.1002/mc.22503
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发表时间：
2017-03
影响因子：
4.6
通讯作者：
Kumar AP
中科院分区：
文献类型：
--
作者：
Gong J;Muñoz AR;Pingali S;Payton-Stewart F;Chan DE;Freeman JW;Ghosh R;Kumar AP
有一种尚未得到满足的需求，即开发新的药物或策略来对抗治疗耐药的胰腺癌(PANCA)。我们实验室最近的研究表明，STAT3负性调节NF-κB，使用NX抑制这一串扰会降低COX-2的转录活性。在临床前动物模型中，抑制这些分子相互作用会阻碍胰腺癌细胞的生长，并减少纤维化。NX是一种从黄柏树皮中提取的提取物，几个世纪以来一直被用作止泻、收敛和抗炎的传统中药。我们假设“NX介导的抑制胰腺癌细胞中的存活分子，如STAT3和NF-κB，将改善传统化疗药物吉西他滨(GEM)的疗效。”因此，我们探索了黄连素的活性成分NX及其衍生物的用途，以增强创业板的作用。使用多个人胰腺癌细胞，我们发现NX和GEM联合处理导致STAT3/NF-κB信号轴蛋白的显着变化，最终以协同方式抑制生长。此外，GEM抗性细胞对NX的敏感性高于其亲本GEM敏感细胞。有趣的是，尽管所使用的NX活性成分黄连素及其衍生物在宝石敏感细胞中具有生物活性，但当它们联合使用时并不能增强宝石的活性。综上所述，这些结果表明，天然提取物NX，而不是其活性成分黄连素，可能通过下调STAT3/NF-κB信号来提高GEM的敏感性。©2016 Wiley期刊，Inc.
There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF‐κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX‐2. Inhibition of these molecular interactions impedes pancreatic cancer cell growth as well as reduces fibrosis in a preclinical animal model. Nx is an extract derived from the bark ofPhellodendron amurenseand has been utilized in traditional Chinese medicine as antidiarrheal, astringent, and anti‐inflammatory agent for centuries. We hypothesized that “Nx‐mediated inhibition of survival molecules like STAT3 and NF‐κB in pancreatic cancer cells will improve the efficacy of the conventional chemotherapeutic agent, gemcitabine (GEM).” Therefore, we explored the utility of Nx, one of its active constituents berberine and its derivatives, to enhance the effects of GEM. Using multiple human pancreatic cancer cells we found that combination treatment with Nx and GEM resulted in significant alterations of proteins in the STAT3/NF‐κB signaling axis culminating in growth inhibition in a synergistic manner. Furthermore, GEM resistant cells were more sensitive to Nx treatment than their parental GEM‐sensitive cells. Interestingly, although berberine, the Nx active component used, and its derivatives were biologically active in GEM sensitive cells they did not potentiate GEM activity when used in combination. Taken together, these results suggest that the natural extract, Nx, but not its active component, berberine, has the potential to improve GEM sensitivity, perhaps by down regulating STAT3/NF‐κB signaling. © 2016 Wiley Periodicals, Inc.
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影响因子：
--
作者：
Alam S;Yadav RS;Pal A;Purshottam SK;Chaudhari BP;Das M;Ansari KM
通讯作者：
Ansari KM
影响因子：
1.9
作者：
Cannillo, Margherita;Frea, Simone;Gaita, Fiorenzo
通讯作者：
Gaita, Fiorenzo
DOI：
10.1016/j.bbamcr.2008.05.020
发表时间：
2008-10-01
影响因子：
5.1
作者：
Mejias-Luque, Raquel;Peiro, Sandra;de Bolos, Carme
通讯作者：
de Bolos, Carme
影响因子：
3.8
作者：
Delitto D;Black BS;Sorenson HL;Knowlton AE;Thomas RM;Sarosi GA;Moldawer LL;Behrns KE;Liu C;George TJ;Trevino JG;Wallet SM;Hughes SJ
通讯作者：
Hughes SJ
影响因子：
3.7
作者：
Kysenius K;Brunello CA;Huttunen HJ
通讯作者：
Huttunen HJ