Aqueous extract of Taxus chinensis var. mairei regulates the Hippo-YAP pathway and promotes apoptosis of non-small cell lung cancer via ATF3 in vivo and in vitro
Aqueous extract of Taxus chinensis var. mairei regulates the Hippo-YAP pathway and promotes apoptosis of non-small cell lung cancer via ATF3 in vivo and in vitro
复制标题
红豆杉的水提取物。
DOI：
10.1016/j.biopha.2021.111506
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Xiaolu Cai
中科院分区：
文献类型：
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作者：
Gaochenxi Zhang;Shuying Dai;Yiyi Chen;Haibin Wang;Ting Chen;Qijin Shu;Shuyi Chen;Liumei Shou;Xiaolu Cai
南方红豆杉（Taxuschinensisvar.mairei，TC）是我国传统的观赏植物和药用植物，其叶和枝条在我国南方地区被广泛用于抗肿瘤治疗。然而，TC水提物（AETC）促进非小细胞肺癌（NSCLC）细胞凋亡的机制和作用尚不清楚。在本研究中，我们观察到AETC抑制了对NSCLC细胞的增殖抑制，并高度抑制了NCI-1975细胞的增殖。此外，AETC对正常人肺上皮细胞产生最小的抑制作用，并诱导NCI-1975和A549细胞凋亡。RNA测序、qRT-PCR、Western blotting和免疫荧光检测结果显示，ATF 3基因表达上调和ATF 3基因敲低分别增强和减弱了AETC的抗肿瘤作用，这与Hippo通路抑制和雅普降解减少有关。此外，AETC减少了裸鼠的肿瘤体积和重量;上调了ATF 3、p-MOB 1和p-YAP（Ser 397）;并积极调节了裂解的PARP和裂解的caspase-9/8/3。这些结果表明AETC通过ATF 3-Hippo-YAP途径在体内和体外诱导NSCLC细胞凋亡。我们还发现AETC对正常细胞和裸鼠无毒性。因此，AETC可能代表一种有前途的抗肿瘤治疗NSCLC的佐剂。
Taxus chinensisvar.mairei(TC) is a traditional Chinese ornamental and medicinal plant, the leaves and twigs of which are used in anti-tumor therapy in southern China. However, the mechanism and role of aqueous extract of TC (AETC) in promoting apoptosis in non-small cell lung cancer (NSCLC) cell lines has remained unclear. In this research, we observed that AETC inhibited the suppression of the proliferation of NSCLC cells and highly inhibited the proliferation of NCI-1975 cells. Furthermore, AETC exerted minimal inhibitory effects on normal human lung epithelial cells and induced apoptosis in NCI-1975 and A549 cells. The findings of RNA sequencing, qRT-PCR, western blotting, and immunofluorescence showed that upregulated ATF3 expression andATF3gene knockdown, respectively, increased and decreased the anti-tumor effects of AETC associated with Hippo pathway inhibition and decreased YAP degradation. Furthermore, AETC reduced the tumor volume and weight in nude mice; upregulated ATF3, p-MOB1, and p-YAP (Ser397); and actively regulated cleaved PARP and cleaved caspase-9/8/3. These findings suggest that AETC induced NSCLC cell apoptosis via the ATF3-Hippo-YAP pathwayin vivoandin vitro. We also found that AETC is non-toxic to normal cells and nude mice. Thus, AETC might represent a promising adjuvant for anti-tumor therapy against NSCLC.