Liu Fujuan, Liu Tao, Li Haiying
Department of Pharmacy, Linyi Fourth People's Hospital, No. 121, Qianshi Ave., Linyi, 276005, Shandong, China.
Department of Pediatrics, Linyi Fourth People's Hospital, No. 121, Qianshi Ave., Linyi, 276005, Shandong, China.
Cancer Cell Int. 2021 Dec 11;21(1):662. doi: 10.1186/s12935-021-02361-5.
Lung cancer has become the leading cause of cancer-related death worldwide and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of cases. Aloperine (ALO), an alkaloid active natural component from S. alopecuroide, has been found to exhibit anti-inflammatory, anti-tumor and anti-viral activity. However, Whether ALO exerts anti-tumor function on NSCLC remains poorly understood, and the underlying mechanisms remain unknown.
The CCK-8, colony formation, cell apoptosis with flow cytometry, wound healing and transwell cell invasion assays, were used to analyze the tumor progression of H1299 and A549 cells treated with ALO in vitro, and the xenograft model was constructed to assess the effect of ALO in vivo. The expression of protein was detected by Western blotting.
ALO suppressed the cell proliferation, self-renewal, migration and invasion, induced apoptosis in A549 and H1299 cell. Furthermore, ALO significantly enhanced the level of cytochrome c in cytosol, and resulted in the dramatical increased levels of the cleaved caspase-3, caspased-9 and PARP. ALO also inhibited the expression of MMP-2 and MMP-9. Additionally, ALO also reduced p-AKT and p-mTOR to attenuate the PI3K/AKT signaling pathway.
This study unveils a rationale for ALO through PI3K/Akt signaling pathway affecting the cell progression such as cell growth, apoptosis and invasion, and ALO acts as a potential chemotherapeutic agent for NSCLC.
肺癌已成为全球癌症相关死亡的主要原因，非小细胞肺癌（NSCLC）约占病例的85%。高刺桐碱（ALO）是一种从高羊茅中提取的具有生物活性的生物碱天然成分，已被发现具有抗炎、抗肿瘤和抗病毒活性。然而，ALO是否对NSCLC发挥抗肿瘤作用仍知之甚少，其潜在机制也尚不清楚。
采用CCK-8法、集落形成实验、流式细胞术检测细胞凋亡、伤口愈合实验和Transwell细胞侵袭实验，分析体外给予ALO处理的H1299和A549细胞的肿瘤进展情况，并构建异种移植模型评估ALO在体内的作用。通过蛋白质印迹法检测蛋白质表达。
ALO抑制A549和H1299细胞的增殖、自我更新、迁移和侵袭，诱导细胞凋亡。此外，ALO显著提高了细胞质中细胞色素c的水平，导致裂解的半胱天冬酶-3、半胱天冬酶-9和PARP水平显著升高。ALO还抑制MMP-2和MMP-9的表达。此外，ALO还降低了p-AKT和p-mTOR的水平，以减弱PI3K/AKT信号通路。
本研究揭示了ALO通过PI3K/Akt信号通路影响细胞生长、凋亡和侵袭等细胞进程的机制，ALO可作为NSCLC的一种潜在化疗药物。
