OBJECTIVE 14-Deoxycoleon U is a natural abietane-type diterpene and exerts an inhibitory effect on tumor cells proliferation, which suggests that 14-Deoxycoleon U may be a potent anti-cancerous lead compound for lung cancer treatment. This study was to evaluate potential of 14-Deoxycoleon U to treat lung adenocarcinoma in vitro and in vivo. METHODS In the present study, the cell viability and apoptosis morphology of 14-Deoxycoleon U-treated A549 and LLC cells were explored using cell counting kit-8 assay and Hoechst 33258 staining. Then, the protein expressions about apoptosis, endoplasmic reticulum (ER) stress, autophagy and cell cycle were measured using Western blot. The autophagosome formation of 14-Deoxycoleon U-treated A549 cells was visualized using a confocal microscopy. LLC lung adenocarcinoma model was established. RESULTS The results indicated that 14-Deoxycoleon U significantly inhibited A549 and LLC cell proliferation in a dose-dependent manner via caspase-dependent apoptosis. Furthermore, apoptosis of both cells was mediated by 14-Deoxycoleon U-induced ER stress. In addition, 14-Deoxycoleon U-induced A549 and LLC cell autophagy, thus promoting their death. Moreover, 14-Deoxycoleon U-induced cell cycle arrest in both cells via inhibition of cyclin D3, cyclin-dependent kinase 6, CDC2 and up-regulation of p21. In vivo results showed that administration of 14-Deoxycoleon U significantly suppressed LLC growth and adverse effects of 14-Deoxycoleon U on organs might be lower than of adriamycin. CONCLUSION Overall, our results demonstrated that 14-Deoxycoleon U represses in vitro and in vivo growth of lung adenocarcinoma through ER stress-mediated apoptosis accompanied by autophagy and cell cycle arrest.

中文翻译：

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14-Deoxycoleon U 诱导的内质网应激介导的肺腺癌细胞凋亡、自噬和细胞周期停滞。

目的 14-Deoxycoleon U 是一种天然松香型二萜，对肿瘤细胞增殖具有抑制作用，这表明 14-Deoxycoleon U 可能是一种有效的肺癌治疗抗癌先导化合物。本研究旨在评估 14-Deoxycoleon U 在体外和体内治疗肺腺癌的潜力。方法 在本研究中，使用细胞计数试剂盒-8 法和 Hoechst 33258 染色来探索 14-脱氧鞘氨醇 U 处理的 A549 和 LLC 细胞的细胞活力和凋亡形态。然后，使用蛋白质印迹法测量细胞凋亡、内质网（ER）应激、自噬和细胞周期的蛋白质表达。使用共聚焦显微镜观察 14-Deoxycoleon U 处理的 A549 细胞的自噬体形成。建立LLC肺腺癌模型。结果结果表明，14-Deoxycoleon U通过半胱天冬酶依赖性细胞凋亡以剂量依赖性方式显着抑制A549和LLC细胞增殖。此外，两种细胞的凋亡均由 14-Deoxycoleon U 诱导的 ER 应激介导。此外，14-Deoxycoleon U 诱导 A549 和 LLC 细胞自噬，从而促进其死亡。此外，14-Deoxycoleon U 通过抑制细胞周期蛋白 D3、细胞周期蛋白依赖性激酶 6、CDC2 和 p21 的上调，在两种细胞中诱导细胞周期停滞。体内结果表明，给予 14-Deoxycoleon U 显着抑制 LLC 生长，并且 14-Deoxycoleon U 对器官的不良影响可能低于阿霉素。结论 总体而言，