双黄升白颗粒治疗骨髓抑制并抑制肺癌进展：从微小RNA角度探讨机制及治疗靶点
Shuanghuang Shengbai granule cures myelosuppression and suppresses lung cancer progression: mechanism and therapeutic targets from the aspect of microRNAs.
作者信息
Wang Shuang, Xu Zhenye, Wang Lifang
机构信息
Department of Oncology II, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Department of Oncology, Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China.
出版信息
Oncotarget. 2017 Jul 10;8(37):62154-62166. doi: 10.18632/oncotarget.19129. eCollection 2017 Sep 22.
BACKGROUND
Shuanghuang Shengbai granule is effective in curing cyclophosphamide-induced myelosuppression without promoting lung cancer development. This study aims to investigate its mechanism and therapeutic targets.
METHODS
Nude mice with lung cancer were treated with physiological saline (control), cyclophosphamide, or cyclophosphamide + Shuanghuang Shengbai. MicroRNA microarray was used to investigate the differentially expressed microRNAs in lung cancer stem cells or bone marrow hematopoietic stem cells between the three groups. MicroRNA expressions were confirmed using quantitative real time-polymerase chain reaction.
RESULTS
Cyclophosphamide suppressed tumor growth and decreased the ratio of SP lung cancer stem cells (P<0.05). Shuanghuang Shengbai further decreased the ratios of SP and CD24IGF1R lung cancer stem cells (P<0.05). Shuanghuang Shengbai completely reversed the cyclophosphamide-induced decreases in white blood cells, proliferation index of bone marrow cells, and the ratio of CD34SCA1 bone marrow hematopoietic stem cells (P<0.05). We found 45 and 343 altered microRNAs for SP lung cancer stem cells and CD34SCA1 bone marrow hematopoietic stem cells, respectively. Moreover, miR-32*, miR-466i-5p, and mmu-miR-669c in SP lung cancer stem cells were confirmed, as well as mmu-miR-106b*, mmu-miR-144, mmu-miR-669k*, mmu-miR-142-3p, mmu-miR-210, and mmu-miR-223 in CD34SCA1 bone marrow hematopoietic stem cells.
CONCLUSION
Shuanghuang Shengbai might promote the proliferation of CD34SCA1 bone marrow hematopoietic stem cells via up-regulating mmu-miR-106b*, mmu-miR-144, and mmu-miR-669k*, as well as down-regulating mmu-miR-142-3p, mmu-miR-210, and mmu-miR-223. Shuanghuang Shengbai might further inhibit the proliferation of SP lung cancer stem cells via enhancing the expressions of miR-32*, miR-466i-5p, and mmu-miR-669c. These might be the mechanism and therapeutic targets of Shuanghuang Shengbai granule.
背景
双黄升白颗粒可有效治疗环磷酰胺诱导的骨髓抑制，且不会促进肺癌发展。本研究旨在探究其作用机制及治疗靶点。
方法
将荷肺癌裸鼠分别用生理盐水（对照组）、环磷酰胺或环磷酰胺+双黄升白进行处理。采用微小RNA芯片研究三组之间肺癌干细胞或骨髓造血干细胞中差异表达的微小RNA。使用定量实时聚合酶链反应确认微小RNA的表达。
结果
环磷酰胺抑制肿瘤生长并降低肺癌干细胞中SP细胞的比例（P<0.05）。双黄升白进一步降低了SP和CD24IGF1R肺癌干细胞的比例（P<0.05）。双黄升白完全逆转了环磷酰胺诱导的白细胞减少、骨髓细胞增殖指数降低以及CD34SCA1骨髓造血干细胞比例降低的情况（P<0.05）。我们分别在SP肺癌干细胞和CD34SCA1骨髓造血干细胞中发现了45个和343个改变的微小RNA。此外，还确认了SP肺癌干细胞中的miR-32*、miR-466i-5p和mmu-miR-669c，以及CD34SCA1骨髓造血干细胞中的mmu-miR-106b*、mmu-miR-144、mmu-miR-669k*、mmu-miR-142-3p、mmu-miR-210和mmu-miR-223。
结论
双黄升白可能通过上调mmu-miR-106b*、mmu-miR-144和mmu-miR-669k以及下调mmu-miR-142-3p、mmu-miR-210和mmu-miR-223来促进CD34SCA1骨髓造血干细胞的增殖。双黄升白可能通过增强miR-32、miR-466i-5p和mmu-miR-669c的表达来进一步抑制SP肺癌干细胞的增殖。这些可能是双黄升白颗粒的作用机制及治疗靶点。
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