The melatonin-MT1 receptor axis modulates tumor growth in PTEN-mutated gliomas.
The melatonin-MT1 receptor axis modulates tumor growth in PTEN-mutated gliomas.
复制标题
褪黑素-MT1受体轴调节PTEN突变神经胶质瘤的肿瘤生长
DOI：
10.1016/j.bbrc.2018.02.010
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Chen Xueran
中科院分区：
文献类型：
--
作者：
Ma Huihui;Wang Zhen;Hu Lei;Zhang Shangrong;Zhao Chenggang;Yang Haoran;Wang Hongzhi;Fang Zhiyou;Wu Lijun;Chen Xueran
超过40%的神经胶质瘤患者患有携带PTEN（在染色体10上缺失的磷酸酶和张力蛋白同源物）突变的肿瘤;这种疾病与较差的治疗抗性和结果相关。这些突变与细胞存活和生长增加、细胞凋亡减少和耐药性有关;因此，迫切需要专注于抑制胶质瘤肿瘤发生和进展的新治疗策略。褪黑激素是一种主要由松果体产生和分泌的吲哚胺，具有多种生理功能，并具有抗氧化和抗肿瘤特性。本研究分析了原代人脑胶质瘤细胞和培养的胶质瘤细胞系中PTEN与褪黑素抑制作用的关系。结果表明，褪黑素在体外和体内均能抑制胶质瘤细胞的生长，这种抑制作用与患者体内PTEN水平有关，而PTEN水平与患者体内MT 1的表达水平显著相关.事实上，c-fos介导的MT 1被证明是褪黑激素对含有野生型PTEN的胶质瘤的作用的关键调节剂。综上所述，这些数据表明，褪黑激素MT 1受体复合物代表了一个潜在的治疗胶质瘤的目标。
More than 40% of glioma patients have tumors that harborPTEN(phosphatase and tensin homologue deleted on chromosome ten) mutations; this disease is associated with poor therapeutic resistance and outcome. Such mutations are linked to increased cell survival and growth, decreased apoptosis, and drug resistance; thus, new therapeutic strategies focusing on inhibiting glioma tumorigenesis and progression are urgently needed. Melatonin, an indolamine produced and secreted predominantly by the pineal gland, mediates a variety of physiological functions and possesses antioxidant and antitumor properties. Here, we analyzed the relationship between PTEN and the inhibitory effect of melatonin in primary human glioma cells and cultured glioma cell lines. The results showed that melatonin can inhibit glioma cell growth both in culture andin vivo.This inhibition was associated with PTEN levels, which significantly correlated with the expression level of MT1 in patients. In fact, c-fos-mediated MT1 was shown to be a key modulator of the effect of melatonin on gliomas that harbor wild typePTEN. Taken together, these data suggest that melatonin-MT1 receptor complexes represent a potential target for the treatment of glioma.