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白藜芦醇通过抑制 STAT3 通路消除骨肉瘤的肿瘤干细胞。

Resveratrol eliminates cancer stem cells of osteosarcoma by STAT3 pathway inhibition.

机构信息

Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

出版信息

PLoS One. 2018 Oct 24;13(10):e0205918. doi: 10.1371/journal.pone.0205918. eCollection 2018.

Abstract

Resveratrol shows potent anti-tumor therapeutic properties in various tumors. However, the exact effect of resveratrol on osteosarcoma cells, especially cancer stem cells, remains unclear. In this study, we examined the effect of resveratrol on osteosarcoma stem cells and explored the underlying molecular mechanisms. Resveratrol inhibited cell viability, self-renewal ability and tumorigenesis of osteosarcoma cells, whereas showed no significant inhibition effects to normal osteoblast cells. Mechanically, resveratrol treatment decreased cytokines synthesis and inhibited JAK2/STAT3 signaling, which was consistent with the decline of cancer stem cells marker, CD133. Exogenous STAT3 activation attenuated the cancer stem cell elimination effects of resveratrol treatment. Our results demonstrated that resveratrol inhibited osteosarcoma cell proliferation and tumorigenesis ability, which was correlated with cytokines inhibition related JAK2/STAT3 signaling blockage. Resveratrol may be a promising therapeutic agent for osteosarcoma management.

摘要

白藜芦醇在各种肿瘤中显示出强大的抗肿瘤治疗特性。然而,白藜芦醇对骨肉瘤细胞,特别是癌干细胞的确切影响尚不清楚。在这项研究中,我们研究了白藜芦醇对骨肉瘤干细胞的影响,并探讨了潜在的分子机制。白藜芦醇抑制骨肉瘤细胞的活力、自我更新能力和致瘤性,而对正常成骨细胞没有明显的抑制作用。机制上,白藜芦醇处理降低了细胞因子的合成,并抑制了 JAK2/STAT3 信号通路,这与癌症干细胞标志物 CD133 的下降一致。外源性 STAT3 激活减弱了白藜芦醇处理对癌症干细胞消除的作用。我们的结果表明,白藜芦醇抑制骨肉瘤细胞的增殖和致瘤能力,这与抑制与 JAK2/STAT3 信号通路阻断相关的细胞因子有关。白藜芦醇可能是骨肉瘤治疗的一种有前途的治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ae9/6200233/ff8704f65b9f/pone.0205918.g001.jpg

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