Siamese crocodile bile induces apoptosis in NCI-H1299 human non-small cell lung cancer cells via a mitochondria-mediated intrinsic pathway and inhibits tumorigenesis.
Siamese crocodile bile induces apoptosis in NCI-H1299 human non-small cell lung cancer cells via a mitochondria-mediated intrinsic pathway and inhibits tumorigenesis.
复制标题
DOI：
10.3892/mmr.2017.6211
复制
发表时间：
2017-04
影响因子：
3.4
通讯作者：
Shen DY
中科院分区：
文献类型：
--
作者：
Tian L;Deng YT;Dong X;Fan JY;Li HL;Ding YM;Peng WX;Chen QX;Shen DY
非小细胞肺癌（NSCLC）是一种广泛且特别侵袭性的癌症形式。具有NSCLC和早期转移的患者通常具有不良预后，突出了对额外药物的迫切需要，以改善手术切除后的疾病结局。本研究旨在确定暹罗鳄鱼胆汁（SCB）是否对NCI-H1299人NSCLC细胞具有抗癌作用。在细胞培养和裸鼠模型中研究SCB的抑制机制。体外实验结果表明，SCB通过阻滞细胞周期和诱导细胞凋亡抑制NCI-H1299细胞的增殖和集落形成能力。线粒体膜电位的丧失和细胞色素c的释放表明SCB处理可能导致NCI-H1299细胞线粒体功能障碍。在分子水平上，SCB改变了Bax/Bcl-2的蛋白表达比例，激活了相关的caspase，提示内在途径参与了SCB诱导的NCI-H1299细胞凋亡。在体内实验中，腹腔注射SCB 4周抑制异种移植瘤生长46.8%，在裸鼠中没有观察到毒性。增殖细胞核抗原和血管内皮生长因子的免疫组化分析也显示，SCB抑制细胞增殖和转移在NSCLC异种移植瘤。总体而言，SCB在体外和体内对NCI-H1299人NSCLC细胞具有抗癌作用，并可能具有治疗人NSCLC的治疗潜力。
Non-small-cell lung cancer (NSCLC) is a widespread and particularly aggressive form of cancer. Patients with NSCLC and early metastases typically have poor prognosis, highlighting the critical need for additional drugs to improve disease outcome following surgical resection. The present study aimed to determine if Siamese crocodile bile (SCB) had an anti-cancer effect on NCI-H1299 human NSCLC cells. The inhibitory mechanism of SCB was examined in cell culture and nude mice. In vitro experimental results revealed that SCB inhibited the proliferation and colony-forming ability of NCI-H1299 cells by arresting cell cycle and inducing apoptosis. The loss of the mitochondrial membrane potential and the release of cytochrome c indicated that SCB treatment may lead to mitochondrial dysfunction in NCI-H1299 cells. At the molecular level, SCB altered the ratio of protein expression of Bax/Bcl-2 and activated associated caspases, suggesting that intrinsic pathway involvement in the SCB-induced apoptosis of NCI-H1299 cells. In the in vivo experiments, intraperitoneal injection of SCB for 4 weeks inhibited xenograft tumor growth by 46.8% without observable toxicity in nude mice. Immunohistochemistry analysis of proliferating cell nuclear antigen and vascular endothelial growth factor also revealed that SCB inhibited cell proliferation and metastasis in NSCLC xenograft tumors. Overall, SCB exerted an anti-cancer effect on NCI-H1299 human NSCLC cells in vitro and in vivo and may have therapeutic potential for the treatment of human NSCLC.