A new gamboge derivative compound 2 inhibits cancer stem-like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma.
A new gamboge derivative compound 2 inhibits cancer stem-like cells via suppressing EGFR tyrosine phosphorylation in head and neck squamous cell carcinoma.
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一种新的藤黄衍生物化合物2通过抑制头颈鳞状细胞癌中的EGFR酪氨酸磷酸化来抑制癌症干细胞样细胞
DOI：
10.1111/jcmm.12129
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发表时间：
2013-11
影响因子：
5.3
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Deng R;Wang X;Liu Y;Yan M;Hanada S;Xu Q;Zhang J;Han Z;Chen W;Zhang P
癌症干细胞样细胞代表导致癌症复发和转移的肿瘤起始细胞群体。传统的抗癌治疗药物通常不能有效消除癌症干细胞样细胞。因此，迫切需要有效靶向癌症干细胞样细胞的新药物或治疗方法来成功治愈癌症。藤黄是一种天然抗癌药物，其药理作用与常规化疗药物不同，能选择性杀伤某些癌细胞。在这项研究中，我们鉴定了一种新的藤黄衍生物，化合物2（C2），它对癌细胞具有显著的抑制作用。有趣的是，当与顺铂（CDDP）相比时，C2有效地抑制头颈部鳞状细胞癌（HNSCC）衍生的癌症干细胞样细胞和非癌症干细胞样细胞的生长，抑制体外肿瘤球和集落的形成，导致HNSCC中多种癌症干细胞（CSC）相关分子的表达丧失。C2能有效抑制裸鼠HNSCC的生长。进一步研究发现，C2显著抑制HNSCC中上皮生长因子受体的活化及其下游蛋白激酶人v-akt鼠胸腺瘤病毒癌基因同源物（AKT）的磷酸化，导致HNSCC中多种CSC相关分子的下调。我们的研究表明，C2能有效抑制HNSCC中肿瘤干细胞样细胞的干细胞样特性，有望成为肿瘤治疗的靶向药物。
Cancer stem-like cells represent a population of tumour-initiating cells that lead to the relapse and metastasis of cancer. Conventional anti-cancer therapeutic drugs are usually ineffective in eliminating the cancer stem-like cells. Therefore, new drugs or therapeutic methods effectively targeting cancer stem-like cells are in urgent need to successfully cure cancer. Gamboge is a natural anti-cancer medicine whose pharmacological effects are different from those of conventional chemotherapeutical drugs and they can kill some kinds of cancer cells selectively. In this study, we identified a new gamboge derivative, Compound 2 (C2), which presents eminent suppression effects on cancer cells. Interestingly, when compared with cisplatin (CDDP), C2 effectively suppresses the growth of both cancer stem-like cells and non-cancer stem-like cells derived from head and neck squamous cell carcinoma (HNSCC), inhibiting the formation of tumour spheres and colony in vitro, resulting in the loss of expression of multiple cancer stem cell (CSC)-related molecules in HNSCC. Treating with C2 effectively inhibited the growth of HNSCC in BALB/C nude mice. Further investigation found that C2 notably inhibits the activation of epithelial growth factor receptor and the phosphorylation of its downstream protein kinase homo sapiens v-akt murine thymoma viral oncogene homolog (AKT) in HNSCC, resulting in down-regulation of multiple CSC-related molecules in HNSCC. Our study has demonstrated that C2 effectively inhibits the stem-like property of cancer stem-like cells in HNSCC and may be a hopeful targeting drug in cancer therapy.
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