State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China.
Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
Cell Prolif. 2018 Aug;51(4):e12458. doi: 10.1111/cpr.12458. Epub 2018 Apr 2.
To investigate the synergistic mechanisms of Paris Saponin II (PSII) and Curcumin (CUR) in lung cancer.
The combination changed the cellular uptake of CUR and PSII, apoptosis, cell cycle arrest and cytokine levels were analysed on different lung cancer cells.
The combination displayed a synergistic anti-cancer effect through promoting the cellular uptake of CUR on different lung cancer cells. Hoechst H33258 staining and FACS assay indicated that the combination of PSII and CUR induced cell cycle arrest and apoptosis. Western blot and cytokine antibody microarray suggested that the combination activated death receptors such as DR6, CD40/CD40L, FasL and TNF-α to induce cancer cells apoptosis, and up-regulated IGFBP-1 leading to inhibition of PI3K/Akt pathway and increase of p21 and p27, which therefore induced a G2 phase arrest in NCI-H446 cells. Meanwhile, the combination suppressed PCNA and NF-κB pathway in 4 kinds of lung cancer cells. They activated the phosphorylation of p38 and JNK, and inhibited PI3K in NCI-H460 and NCI-H446 cells, enhanced the phosphorylation of JNK in NCI-H1299 cells, and increased the phosphorylation of p38 and ERK, and suppressed PI3K in NCI-H520 cells.
PSII combined with CUR had a synergistic anti-cancer effect on lung cancer cells. These findings provided a rationale for using the combination of curcumin and PSII in the treatment of lung cancer in future.
研究白头翁皂苷 II(PSII)和姜黄素(CUR)在肺癌中的协同作用机制。
改变 CUR 和 PSII 的细胞摄取,分析不同肺癌细胞的细胞凋亡、细胞周期阻滞和细胞因子水平。
该联合通过促进不同肺癌细胞对 CUR 的细胞摄取显示出协同的抗癌作用。Hoechst H33258 染色和 FACS 分析表明,PSII 和 CUR 的联合诱导细胞周期阻滞和细胞凋亡。Western blot 和细胞因子抗体微阵列表明,联合激活了死亡受体,如 DR6、CD40/CD40L、FasL 和 TNF-α,诱导癌细胞凋亡,并上调 IGFBP-1,从而抑制 PI3K/Akt 通路,增加 p21 和 p27,导致 NCI-H446 细胞 G2 期阻滞。同时,联合抑制了 4 种肺癌细胞中的 PCNA 和 NF-κB 通路。它们激活了 NCI-H460 和 NCI-H446 细胞中 p38 和 JNK 的磷酸化,抑制了 PI3K,增强了 NCI-H1299 细胞中 JNK 的磷酸化,增加了 p38 和 ERK 的磷酸化,并抑制了 NCI-H520 细胞中的 PI3K。
PSII 联合 CUR 对肺癌细胞具有协同抗癌作用。这些发现为未来使用 CUR 和 PSII 的联合治疗肺癌提供了依据。