Curcumin and metformin-mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells
Curcumin and metformin-mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells
复制标题
DOI：
10.1002/mc.22692
复制
发表时间：
2017-11-01
影响因子：
4.6
通讯作者：
Kuriakose, Moni A.
中科院分区：
文献类型：
--
作者：
Siddappa, Gangotri;Kulsum, Safeena;Kuriakose, Moni A.
有效的化学预防对于改善口腔癌的预后至关重要。据报道，姜黄素和二甲双胍作为单一药物在体外以及口腔癌患者中表现出化学预防特性。在本研究中，在4-硝基喹啉-1-氧化物（4 NQO）诱导的小鼠口腔癌发生模型中测试了该药物组合的化学预防功效。分子分析揭示了该模型中癌症干细胞（CSC）驱动的口腔致癌进展，其中在转录物（40-100倍）和蛋白质水平（P0.0001），从第8周至第25周观察到CSC特异性标志物（CD 44和CD 133）的表达进行性增加。在第17周用姜黄素和二甲双胍对动物进行化学预防性治疗表明，与对照组相比，联合方案降低了肿瘤体积（0.69 ± 0.03 vs 6.66 ± 2.4mm（3）; P=0.04），并改善了动物的总体存活率（P=0.03）。分子状态的评估显示，与未处理的对照组相比，处理组中CSC标志物的总体下调。此外，对4 NQO诱导的小鼠组织的进行性阶段产生的原代细胞的治疗的体外评估显示，联合治疗后CSC标志物的一致性和一致性下调（P
Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4-nitro quinoline-1-oxide (4NQO) induced mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40-100-fold) and protein levels (P0.0001). Chemopreventive treatment of the animals at 17th week with curcumin and metformin indicated that the combination regimen decreased tumor volume when compared to the control arm (0.69+0.03 vs 6.66+2.4mm(3); P=0.04) and improved overall survival of the animals (P=0.03). Assessment of the molecular status showed an overall downregulation of CSC markers in the treatment arms as compared to the untreated control. Further, in vitro assessment of the treatment on the primary cells generated from progressive stages of 4NQO-induced mice tissue showed a concordant and consistent downregulation of the CSC markers following combination treatment (P