天然产物助力西妥昔单抗
创作:Lexi 审核:Lexi 2019年11月11日
  • 牛樟芝(AC)的新型泛醌衍生物AC009降低人结直肠癌(CRC)细胞系(HCT116、RKO、DLD-1和SW480)的活力;
  • AC009处理导致HCT116细胞周期阻滞/凋亡,这些作用或通过caspase和Bcl-2信号通路发生;
  • AC009显著抑制小鼠异种移植瘤生长;
  • AC009或通过影响miRNA表达,从而调控突变KRAS基因的表达;
  • AC009降低肿瘤干细胞标志物CD44/CD24在KRAS突变CRC中的表达,并恢复西妥昔单抗的抑癌作用;
  • miRNA-27a可恢复西妥昔单抗对KRAS突变CRC细胞的抑制。
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Lexi
结直肠癌(CRC)是台湾最常见的死因之一。以往的研究表明,牛樟芝(AC)可用于治疗中毒、腹泻和癌症。最新发表在Cancers杂志的一项研究纯化了一种新型泛醌衍生物AC009,并对其抗肿瘤活性进行了研究。该研究发现AC009或可通过caspase和Bcl-2通路阻滞CRC细胞系的细胞周期,并诱导凋亡。此外,AC009或通过影响miRNA表达从而调控突变KRAS基因的表达,并恢复西妥昔单抗的抑癌作用。
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Cancers [IF:6.162]

Novel Antrodia cinnamomea Extract Reduced Cancer Stem-Like Phenotype Changes and Resensitized KRAS-Mutant Colorectal Cancer via a MicroRNA-27a Pathway

新型牛樟芝提取物减少癌症干细胞样表型改变,并通过MicroRNA-27a通路重建KRAS突变型结直肠癌对西妥昔单抗的敏感性

10.3390/cancers11111657

2019-10-26, Article

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Abstract:收起
Colorectal cancer (CRC) is one of the most common causes of death in Taiwan. Previous studies showed that Antrodia cinnamomea (AC) can treat poisoning, diarrhea, and various types of cancer. Therefore, we purified a novel ubiquinone derivative, AC009, and investigated its antitumor effects. Cell viability assays revealed that AC009 reduced the viability of several human CRC cell lines. AC009 treatment resulted in cell-cycle arrest/apoptosis, and these effects may occur via caspase and Bcl-2 signaling pathways. We demonstrated that AC009 could significantly inhibit in vivo tumor growth in xenograft mouse models. Using messenger RNA (mRNA) and microRNA (miRNA) microarrays, we found that KRAS gene expression was also regulated by AC009, possibly through specific miRNAs. AC009 also reduced cancer stem-cell marker CD44+/CD24+ expression and restored the tumor inhibition effect of cetuximab in KRAS-mutant CRC. Moreover, we found that miRNA-27a could restore the tumor inhibition effect of cetuximab in KRAS-mutant CRC cells. Taken together, our results suggest that AC009 has therapeutic potential against human wild-type and KRAS-mutant CRC.

First Authors:
Tsung-Jen Lin

Correspondence Authors:
Ching-Hu Chung

All Authors:
Tsung-Jen Lin,Kuo-Chu Lai,An-Sheng Lee,Chien-Hsin Chang,Chiung-Lin Liu,Ching-Hu Chung

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