Triptolide inhibits cell growth and GRP78 protein expression but induces cell apoptosis in original and radioresistant NPC cells.
Triptolide inhibits cell growth and GRP78 protein expression but induces cell apoptosis in original and radioresistant NPC cells.
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雷公藤甲素在原始和抗辐射的鼻咽癌细胞中抑制细胞生长和 GRP78 蛋白表达，但诱导细胞凋亡
DOI：
10.18632/oncotarget.10412
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发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Feng X
中科院分区：
文献类型：
--
作者：
Li C;Zhang B;Lv W;Lai C;Chen Z;Wang R;Long X;Feng X
放射抵抗是影响鼻咽癌疗效和生存的关键因素。天然雷公藤内酯醇（TPL）已被发现可规避肿瘤的耐药效应，但其对鼻咽癌放射抗性的影响研究甚少。本研究以10个抗Gy CNE 2亚克隆（CNE 2-SR）作为鼻咽癌辐射抗性模型。MTT法测定TPL对CNE 2和CNE 2-SR细胞的半数抑制浓度（IC 50），流式细胞仪检测细胞周期，Western blot检测蛋白表达。TPL处理CNE 2和CNE 2-SR细胞的IC_（50）分别为23.6 ± 1.41 nmol/L和31.2 ± 1.16 nmol/L。6戈伊X射线对CNE 2的作用是中等剂量，25 nM TPL与CNE 2和CNE 2-SR的IC 50值接近，6戈伊X射线和/或25 nM TPL均能显著抑制裸鼠移植瘤的生长。此外，6戈伊X射线和/或25 nM TPL显著抑制CNE 2和CNE 2-SR细胞的生长，诱导细胞凋亡和M/G2期阻滞。此外，TPL处理显著抑制CNE 2和CNE 2-SR细胞中GRP 78蛋白的表达。这些结果表明，TPL可能作为一个潜在的放射增敏剂治疗鼻咽癌。
The radioresistance is the key factor to hamper curative effect and survival of nasopharyngeal carcinoma (NPC) patients. Nature triptolide (TPL) has been found to circumvent drug-resistant effect of cancer, but its effect on NPC radioresistance has been rarely studied. In the present study, the 10 Gy-resistant CNE2 subclones (CNE2-SR) were used as a NPC radioresistant model. The IC50 of TPL in CNE2 and CNE2-SR cells was measured by MTT assay, cell cycle was analyzed by flow cytometry, and protein expression was examined by western blot. Our data showed that TPL treatment decreased the percentage of viable cells, and IC50 value in CNE2 and CNE2-SR cells was 23.6 ± 1.41 nmol/L and 31.2 ± 1.16 nmol/L, respectively. Six Gy was a moderate dosage of X-ray for CNE2, and 25 nM TPL was close to IC50 value of CNE2 and CNE2-SR. Six Gy X-ray and/or 25 nM TPL significantly inhibited tumor growth in nude mice. Furthermore, 6 Gy X-ray and/or 25 nM TPL significantly inhibited cell growth and induced cell apoptosis and M/G2 phase arrest in CNE2 and CNE2-SR cells. Moreover, TPL treatment significantly inhibited the expression of GRP78 protein in CNE2 and CNE2-SR cells. These results suggest that TPL may serve as a potential radiosensitizer agent for NPC treatment.