Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an 710038, China.
Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
Int J Biol Sci. 2019 Jun 4;15(8):1637-1653. doi: 10.7150/ijbs.33790. eCollection 2019.
Butein, a member of the chalcone family, is a potent anticarcinogen against multiple cancers, but its specific anti-NSCLC mechanism remains unknown. The present study examined the effects of butein treatment on NSCLC cell lines and NSCLC xenografts. Butein markedly decreased NSCLC cell viability; inhibited cell adhesion, migration, invasion, and colony forming ability; and induced cell apoptosis and G2/M phase arrest in NSCLC cells. Moreover, butein significantly inhibited PC-9 xenograft growth. Both and studies verified that butein exerted anti-NSCLC effect through activating endoplasmic reticulum (ER) stress-dependent reactive oxygen species (ROS) generation. These pro-apoptotic effects were reversed by the use of 4- phenylbutyric acid (4-PBA), CHOP siRNA, N-acetyl-L-cysteine (NAC) and Z-VAD-FMK (z-VAD) Moreover, inhibition of ER stress markedly reduced ROS generation. In addition, studies further confirmed that inhibition of ER stress or oxidative stress partially abolished the butein-induced inhibition of tumor growth. Therefore, butein is a potential therapeutic agent for NSCLC, and its anticarcinogenic action might be mediated by ER stress-dependent ROS generation and the apoptosis pathway.
白杨素是查尔酮家族的一员，是一种针对多种癌症的有效抗癌剂，但它对非小细胞肺癌的具体抗癌机制尚不清楚。本研究探讨了白杨素处理对非小细胞肺癌细胞系和非小细胞肺癌异种移植瘤的影响。白杨素显著降低非小细胞肺癌细胞活力；抑制细胞黏附、迁移、侵袭和集落形成能力；并诱导非小细胞肺癌细胞凋亡和 G2/M 期阻滞。此外，白杨素显著抑制 PC-9 异种移植瘤的生长。体内和体外研究均证实，白杨素通过激活内质网（ER）应激依赖性活性氧（ROS）生成发挥抗非小细胞肺癌作用。这些促凋亡作用可被 4-苯基丁酸（4-PBA）、CHOP siRNA、N-乙酰-L-半胱氨酸（NAC）和 Z-VAD-FMK（z-VAD）逆转。此外，抑制 ER 应激显著减少 ROS 生成。此外，体内研究进一步证实，抑制 ER 应激或氧化应激部分消除了白杨素诱导的肿瘤生长抑制。因此，白杨素是一种有潜力的非小细胞肺癌治疗药物，其抗癌作用可能是通过 ER 应激依赖性 ROS 生成和凋亡途径介导的。
