Inhibition of cancer stem cell like cells by a synthetic retinoid.
Inhibition of cancer stem cell like cells by a synthetic retinoid.
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合成类维生素A抑制癌症干细胞样细胞
DOI：
10.1038/s41467-018-03877-7
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发表时间：
2018-04-11
影响因子：
16.6
通讯作者：
Yu B
中科院分区：
文献类型：
--
作者：
Chen J;Cao X;An Q;Zhang Y;Li K;Yao W;Shi F;Pan Y;Jia Q;Zhou W;Yang F;Wei F;Wang N;Yu B
开发可消除恶性肿瘤的生长和转移的新型药物是癌症研究人员的主要挑战，我们描述了一种新型的合成性类维生素类线皮，即WYC-209，它抑制了恶性鼠类黑色素瘤肿瘤肿瘤肿瘤重复的细胞（TRC）的繁殖。人黑色素瘤TRC的肺部，肺癌症，卵巢癌和乳腺癌的培养很有趣。拮抗剂或与RAR siRNAS阻滞或减少抑制作用该分子的作用表明分子的靶标为RAR。新的类维克因WYC-209治疗恶性黑色素瘤肿瘤效率高，毒性很少。
在这里发现有效的药物是癌症治疗的主要挑战，作者报告了由视黄肿瘤的抗肿瘤和抗转移活性的合成性类维生素类动物。
Developing novel drugs that can abrogate the growth and metastasis of malignant tumors is a major challenge for cancer researchers. Here we describe a novel synthetic retinoid, namely WYC-209, which inhibits proliferation of malignant murine melanoma tumor-repopulating cells (TRCs), known to resist conventional drug treatment, with an IC50of 0.19 μM in a dose-dependent manner. WYC-209 also inhibits proliferation of TRCs of human melanoma, lung cancer, ovarian cancer, and breast cancer in culture. Interestingly, the treated TRCs fail to resume growth even after the drug washout. Importantly, the molecule abrogates 87.5% of lung metastases of melanoma TRCs in immune-competent wild-type C57BL/6 mice at 0.22 mg kg−1without showing apparent toxicity. Pretreating the melanoma TRCs with retinoic acid receptor (RAR) antagonists or with RAR siRNAs blocks or reduces the inhibitory effect of the molecule, suggesting that the target of the molecule is RAR. WYC-209 induces TRC apoptosis and pretreating the TRCs with caspase 3 inhibitor or depleting caspase 3 with siRNAs substantially rescues growth of TRCs from WYC-209 inhibition, suggesting that WYC-209 induces TRCs apoptosis primarily via the caspase 3 pathway. Our findings demonstrate the promise of the new retinoid WYC-209 in treating malignant melanoma tumors with high efficacy and little toxicity.
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影响因子：
4.6
作者：
Chen J;Zhou W;Jia Q;Chen J;Zhang S;Yao W;Wei F;Zhang Y;Yang F;Huang W;Zhang Y;Zhang H;Zhang Y;Huang B;Zhang Z;Jia H;Wang N
通讯作者：
Wang N
影响因子：
4.8
作者：
Shih, Michelle Y. S.;Kane, Maureen A.;Farese, Robert V., Jr.
通讯作者：
Farese, Robert V., Jr.
影响因子：
41.2
作者：
通讯作者：
--
影响因子：
64.8
作者：
Enari, M;Talanian, RV;Nagata, S
通讯作者：
Nagata, S
影响因子：
158.5
作者：
Tallman, MS;Andersen, JW;Wiernik, PH
通讯作者：
Wiernik, PH