Li Chi-Cheng, Lu Cheng-You, Hsu Chiung-Hung, Hsieh Dennis Jine-Yuan, Wang Tso-Fu, Ho Tsung-Jung, Kuo Wei-Wen, Day Cecilia Hsuan, Liao Shih-Chieh, Chen Ming-Cheng, Huang Chih-Yang
Center of Stem Cell and Precision Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; College of Medicine, Tzu Chi University, Hualien, Taiwan.
Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
Chin J Physiol. 2023 Jul-Aug;66(4):189-199. doi: 10.4103/cjop.CJOP-D-23-00009.
Lung cancer is the most common malignant cancer worldwide. Combination therapies are urgently needed to increase patient survival. Calycosin is a phytoestrogen isoflavone that has been reported previously to inhibit tumor cell growth, although its effects on lung cancer remain unclear. The aim of this study was to investigate the effects of calycosin on cell proliferation and apoptosis of gemcitabine-resistant lung cancer cells. Using calycosin to treat human lung cancer cells (CL1-0) and gemcitabine-resistant lung cancer cells (CL1-0 GEMR) and examine the effects on the cells. Cultured human lung cancer cells (CL1-0) and gemcitabine-resistant lung cancer cells (CL1-0 GEMR) were treated with increasing concentrations of calycosin. Cell viability and apoptosis were studied by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide, flow cytometry, and TUNEL assays. Western blots were used to measure the expression levels of proliferation-related proteins and cancer stem cell proteins in CL1-0 GEMR cells. The results showed that calycosin treatment inhibited cell proliferation, decreased cell migration ability, and suppressed cancer stem cell properties in CL1-0 GEMR cells. Interestingly, in CL1-0 GEMR cells, calycosin treatment not only increased LDOC1 but also decreased GNL3L/NFκB protein levels and mRNA levels, in concentration-dependent manners. We speculate that calycosin inhibited cell proliferation of the gemcitabine-resistant cell line through regulating the LDOC1/GNL3L/NFκB pathway.
肺癌是全球最常见的恶性肿瘤。迫切需要联合治疗来提高患者生存率。毛蕊异黄酮是一种植物雌激素异黄酮，此前有报道称其可抑制肿瘤细胞生长，但其对肺癌的影响尚不清楚。本研究旨在探讨毛蕊异黄酮对吉西他滨耐药肺癌细胞增殖和凋亡的影响。用毛蕊异黄酮处理人肺癌细胞（CL1-0）和吉西他滨耐药肺癌细胞（CL1-0 GEMR），并检测其对细胞的影响。用不同浓度的毛蕊异黄酮处理培养的人肺癌细胞（CL1-0）和吉西他滨耐药肺癌细胞（CL1-0 GEMR）。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法、流式细胞术和TUNEL法研究细胞活力和凋亡情况。用蛋白质免疫印迹法检测CL1-0 GEMR细胞中增殖相关蛋白和癌症干细胞蛋白的表达水平。结果显示，毛蕊异黄酮处理可抑制CL1-0 GEMR细胞的增殖，降低细胞迁移能力，并抑制其癌症干细胞特性。有趣的是，在CL1-0 GEMR细胞中，毛蕊异黄酮处理不仅使LDOC1增加，还以浓度依赖的方式降低了GNL3L/NFκB蛋白水平和mRNA水平。我们推测毛蕊异黄酮通过调节LDOC1/GNL3L/NFκB通路抑制吉西他滨耐药细胞系的细胞增殖。
