Parthenolide inhibits cancer stem-like side population of nasopharyngeal carcinoma cells via suppression of the NF-κB/COX-2 pathway.
Parthenolide inhibits cancer stem-like side population of nasopharyngeal carcinoma cells via suppression of the NF-κB/COX-2 pathway.
复制标题
小白菊内酯通过抑制 NF-kappaB/COX-2 通路抑制鼻咽癌细胞的癌干样侧群
作者：
Liao K;Xia B;Zhuang QY;Hou MJ;Zhang YJ;Luo B;Qiu Y;Gao YF;Li XJ;Chen HF;Ling WH;He CY;Huang YJ;Lin YC;Lin ZN
肿瘤干细胞在鼻咽癌的发病机制中起核心作用，并有助于疾病的发生和复发。本研究发现，环氧化酶-2（cyclooxygenase-2，考克斯-2）可调控鼻咽癌细胞的癌干细胞样侧群细胞，增强癌干细胞样细胞的特性，如更高的集落形成效率和干细胞相关基因的过表达。考克斯-2对肿瘤干细胞样特征的调节作用可能是由ABCG 2介导的。通过功能获得性实验，考克斯-2过表达增加了侧群细胞的比例及其癌症干细胞特性。本研究还表明，与经典化疗药物5-氟尿嘧啶，增加侧群细胞的比例和上调考克斯-2的表达，parthenoprene，一种天然存在的小分子，优先针对鼻咽癌细胞的侧群细胞和下调考克斯-2。此外，我们还发现考克斯-2抑制剂NS-398和CAY 10404以及siRNA和shRNA敲除考克斯-2均能抑制肿瘤干细胞样细胞的表型。这些发现表明，考克斯-2抑制是银胶菊诱导鼻咽癌癌干细胞样细胞死亡的机制。此外，孤雌菊还通过抑制IκB激酶复合物的磷酸化和IκBα的降解，抑制核因子-κ B（NF-κB）核转位。综上所述，这些结果表明孤雌菊可能通过NF-κB/考克斯-2途径发挥其肿瘤干细胞靶向化疗作用。
Cancer stem cells play a central role in the pathogenesis of nasopharyngeal carcinoma and contribute to both disease initiation and relapse. In this study, cyclooxygenase-2 (COX-2) was found to regulate cancer stem-like side population cells of nasopharyngeal carcinoma cells and enhance cancer stem-like cells' characteristics such as higher colony formation efficiency and overexpression of stemness-associated genes. The regulatory effect of COX-2 on cancer stem-like characteristics may be mediated by ABCG2. COX-2 overexpression by a gain-of-function experiment increased the proportion of side population cells and their cancer stemness properties. The present study also demonstrated that in contrast to the classical chemotherapy drug 5-fluorouracil, which increased the proportion of side population cells and upregulated the expression of COX-2, parthenolide, a naturally occurring small molecule, preferentially targeted the side population cells of nasopharyngeal carcinoma cells and downregulated COX-2. Moreover, we found that the cancer stem-like cells' phenotype was suppressed by using COX-2 inhibitors NS-398 and CAY10404 or knocking down COX-2 with siRNA and shRNA. These findings suggest that COX-2 inhibition is the mechanism by which parthenolide induces cell death in the cancer stem-like cells of nasopharyngeal carcinoma. In addition, parthenolide exhibited an inhibitory effect on nuclear factor-kappa B (NF-κB) nucler translocation by suppressing both the phosphorylation of IκB kinase complex and IκBα degradation. Taken together, these results suggest that parthenolide may exert its cancer stem cell-targeted chemotherapy through the NF-κB/COX-2 pathway.
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影响因子：
20.3
作者：
Guzman, ML;Neering, SJ;Jordan, CT
通讯作者：
Jordan, CT
影响因子：
4.1
作者：
Ma, Hsin-I;Chiou, Shih-Hwa;Sytwu, Huey-Kang
通讯作者：
Sytwu, Huey-Kang
影响因子：
20.3
作者：
Guzman, ML;Rossi, RM;Jordan, CT
通讯作者：
Jordan, CT
影响因子：
7.3
作者：
Habeeb, AG;Rao, PNP;Knaus, EE
通讯作者：
Knaus, EE
影响因子：
9.3
作者：
Annabi B;Laflamme C;Sina A;Lachambre MP;Béliveau R
通讯作者：
Béliveau R