| 刘晓丹,詹晓峰,尚韬.甘草水提物诱导结直肠癌细胞铁死亡的作用及机制研究[J].浙江中西医结合杂志,2026,36(2): |
| 甘草水提物诱导结直肠癌细胞铁死亡的作用及机制研究 |
| Licorice Extract Induces Ferroptosis in Colorectal Cancer Cells Mechanisms and Therapeutic Effects |
| 投稿时间：2025-06-19 修订日期：2025-09-23 |
| DOI： |
| 中文关键词: 甘草水提物，p53-YAP1通路，CRC细胞，铁死亡 |
| 英文关键词:Licorice extract P53-YAP1 pathway CRC cells ferroptosis |
| 基金项目:浙江省中医药科技计划项目 |
|
| 摘要点击次数: 70 |
| 全文下载次数: 0 |
| 中文摘要: |
| 目的 探究甘草水提物（licorice extracts, LE）能否通过调控铁死亡关键通路影响结直肠癌细胞活力。方法 将SW837细胞根据随机数字表法分为空白组、LE低剂量组、LE高剂量组、LE高剂量+Erastin组、LE高+Erastin+L组（Erastin为铁死亡激动剂、liproxstatin-1为铁死亡抑制剂，分组中以L简写）。细胞计数试剂盒8（CCK8）检测细胞活力；酶联免疫吸附试验（ELISA）检测脂质过氧化物（MDA）含量、Fe2+含量；钙黄绿素淬灭法检测不稳定铁池（LIP）水平；实时荧光定量多聚核苷酸链式反应（qPCR）检测谷胱甘肽过氧化物酶4（GPX4）、溶质载体家族7成员11（SLC7A11）mRNA表达水平；蛋白质免疫印迹检测Yes相关蛋白1（YAP1）、长链酯酰辅酶A合成酶4（ACSL4）、SLC7A11蛋白表达水平。结果 与空白组比较，LE高剂量、LE高剂量+Erastin组的细胞活性[(58.85±5.58)、(45.30±4.63)比(100.00±10.78)，P<0.01]显著降低；MDA含量[(11.05±0.92)、(16.75±1.80)比(5.02±0.47)，P<0.01]、Fe2+含量[(2.42±0.22)、(3.20±0.32)比(1.0±0.10)，P<0.01]、LIP水平[(2.45±0.25)、(3.87±0.37)比(1.00±0.12)，P<0.01]显著升高；GPX4[(0.767±0.065)、(0.668±0.054)比(1.003±0.098)，P<0.05、P<0.01]、SLC7A11[(0.746±0.068)、(0.530±0.058)比(1.003±0.092)，P<0.05、P<0.01] mRNA表达水平显著降低；YAP1[(1.499±0.105)、(1.753±0.106)比(1.000±0.109)，P<0.01]、ACSL4[(1.725±0.102)、(2.109±0.093)比(1.000±0.099)，P<0.01]蛋白表达水平显著升高，SLC7A11 [(0.541±0.103)、(0.281±0.104)比(1.000±0.104)，P<0.01] 蛋白表达水平显著降低。与LE高剂量+Erastin组比较，加入铁死亡抑制剂后，SW837细胞活性[(90.83±8.61)比(45.30±4.63)，P<0.01]显著升高；MDA含量[(5.51±0.60)比(16.75±1.80)，P<0.01]、Fe2+含量[(1.12±0.14)比(3.20±0.32)，P<0.01]、LIP水平[(1.10±0.13)比(3.87±0.37)，P<0.01]显著降低；GPX4[(0.863±0.083)比(0.668±0.054)，P<0.05]、SLC7A11[(0.900±0.088)比(0.530±0.058)，P<0.01] mRNA表达水平显著升高；YAP1[(0.903±0.104)比(1.753±0.106)，P<0.01]、ACSL4[(0.943±0.094)比(2.109±0.093)，P<0.01]蛋白表达水平显著降低，SLC7A11[(0.886±0.093)比(0.281±0.104)，P<0.01]蛋白表达水平显著升高。结论 LE可通过调控铁死亡关键分子如YAP1通路诱导结直肠癌细胞发生铁死亡。 |
| 英文摘要: |
| Objective To investigate whether licorice extracts (LE) can affect colorectal cancer cell viability by regulating key ferroptosis pathways. Methods SW837 cells were randomly divided into five groups using a random number table method: control group, low-dose LE group, high-dose LE group, high-dose LE + Erastin group, and high-dose LE + Erastin + Liproxstatin-1 (L) group (where Erastin is a ferroptosis agonist and Liproxstatin-1 is a ferroptosis inhibitor). Cell viability was measured using the Cell Counting Kit-8 (CCK-8) assay; malondialdehyde (MDA) content and Fe2? levels were detected by enzyme-linked immunosorbent assay (ELISA); the labile iron pool (LIP) level was determined using the calcein quenching method; mRNA expression levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were measured by quantitative real-time polymerase chain reaction (qPCR); protein expression levels of Yes-associated protein 1 (YAP1), long-chain acyl-CoA synthetase 4 (ACSL4), and SLC7A11 were detected by Western blot. Results Compared with the control group, the high-dose LE group and the high-dose LE + Erastin group showed significantly reduced cell viability [(58.85 ± 5.58), (45.30 ± 4.63) vs. (100.00 ± 10.78), P<0.01]; significantly increased MDA content [(11.05 ± 0.92), (16.75 ± 1.80) vs. (5.02 ± 0.47), P<0.01], Fe2? content [(2.42 ± 0.22), (3.20 ± 0.32) vs. (1.0 ± 0.10), P<0.01], and LIP levels [(2.45 ± 0.25), (3.87 ± 0.37) vs. (1.00 ± 0.12), P<0.01]; significantly decreased mRNA expression of GPX4 [(0.767 ± 0.065), (0.668 ± 0.054) vs. (1.003 ± 0.098), P<0.05, P<0.01] and SLC7A11 [(0.746 ± 0.068), (0.530 ± 0.058) vs. (1.003 ± 0.092), P<0.05, P<0.01]; significantly increased protein expression of YAP1 [(1.499 ± 0.105), (1.753 ± 0.106) vs. (1.000 ± 0.109), P<0.01] and ACSL4 [(1.725 ± 0.102), (2.109 ± 0.093) vs. (1.000 ± 0.099), P<0.01]; and significantly decreased protein expression of SLC7A11 [(0.541 ± 0.103), (0.281 ± 0.104) vs. (1.000 ± 0.104), P<0.01]. Compared with the high-dose LE + Erastin group, the addition of the ferroptosis inhibitor (Liproxstatin-1) significantly increased SW837 cell viability [(90.83 ± 8.61) vs. (45.30 ± 4.63), P<0.01]; significantly decreased MDA content [(5.51 ± 0.60) vs. (16.75 ± 1.80), P<0.01], Fe2? content [(1.12 ± 0.14) vs. (3.20 ± 0.32), P<0.01], and LIP levels [(1.10 ± 0.13) vs. (3.87 ± 0.37), P<0.01]; significantly increased mRNA expression of GPX4 [(0.863 ± 0.083) vs. (0.668 ± 0.054), P<0.05] and SLC7A11 [(0.900 ± 0.088) vs. (0.530 ± 0.058), P<0.01]; significantly decreased protein expression of YAP1 [(0.903 ± 0.104) vs. (1.753 ± 0.106), P<0.01] and ACSL4 [(0.943 ± 0.094) vs. (2.109 ± 0.093), P<0.01]; and significantly increased protein expression of SLC7A11 [(0.886 ± 0.093) vs. (0.281 ± 0.104), P<0.01]. Conclusion LE can induce ferroptosis in colorectal cancer cells by modulating key ferroptosis-related molecules, including the YAP1 pathway. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
