| 吕仙梅,郭秋生.雷公藤内酯酮通过调控Wnt/β-catenin信号通路诱导三阴性乳腺癌细胞 凋亡与自噬[J].浙江中西医结合杂志,2024,34(12): |
| 雷公藤内酯酮通过调控Wnt/β-catenin信号通路诱导三阴性乳腺癌细胞 凋亡与自噬 |
| Triptonide induces apoptosis and autophagy in triple negative breast cancer cells by regulating Wnt/β-catenin signal pathway |
| 投稿时间：2024-03-13 修订日期：2024-11-21 |
| DOI： |
| 中文关键词: 三阴性乳腺癌 雷公藤内酯酮 凋亡 自噬 Wnt/β-Catenin信号通路 |
| 英文关键词:TNBC Triptonide apoptosis autophagy Wnt/ β-Catenin signal pathway |
| 基金项目:金华市中医药科技计划项目(基金号：2024LC11) |
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| 中文摘要: |
| 摘 要：目的 研究雷公藤内酯酮（Triptonide，Tpn）对人三阴性乳腺癌（Triple negative breast cancer，TNBC）细胞凋亡和自噬的诱导作用及其分子机制。方法 采用细胞增殖-毒性检测（Cell Counting Kit-8，CCK-8）、克隆形成、Transwell、流式细胞术等实验，分析Tpn对TNBC细胞株MDA-MB-231和MDA-MB-453细胞的增殖、侵袭、凋亡和自噬的影响；利用免疫印迹（Western blot，WB）实验，检测Tpn对MDA-MB-231和MDA-MB-453细胞中Wnt家族成员3a（Wnt 3a）、β-连环蛋白（β-catenin）、切割型半胱氨酸蛋白酶-3（Cle-Caspase-3）、聚腺苷二磷酸核糖聚合酶降解产物（Cle-PARP）、自噬调控因子Beclin-1、p62、微管相关蛋白1轻链3（LC-3）等蛋白质的影响。结果 不同浓度的Tpn（10 nm/L、20 nm/L、40 nm/L）能够抑制MDA-MB-231和MDA-MB-453细胞株的克隆形成能力（48h抑制率分别为39.67%、60.33%、79.14%和44.33%、52.34%、77.67%），以及侵袭能力（48h抑制率分别为26.33%、33.67%、45.67%和9.33%、15.34%、66.33%），并能诱导细胞凋亡（48h凋亡率分别为10.06%、12.66%、18.76%和8.70%、15.09%、19.18%）。分子机制实验结果表明，Tpn处理MDA-MB-231和MDA-MB-453细胞后，Wnt 3a、β-catenin、p62等蛋白质的表达显著减少，而Cle-Caspase-3、Cle-PARP、Beclin-1等蛋白质的表达以及LC3 II/I比值显著增加。结 论 Tpn能够抑制MDA-MB-231和MDA-MB-453细胞的克隆形成和侵袭能力，并诱导细胞凋亡和自噬。这一机制可能是通过调控Wnt/β-catenin信号通路实现的。 |
| 英文摘要: |
| ABSTRACT:Objective Investigating the inducive effects of Triptonide (Tpn) on apoptosis and autophagy in human triple-negative breast cancer (TNBC) cells and its underlying molecular mechanisms.Methods Using CCK-8, colony formation, Transwell, and flow cytometry assays, we analyzed the effects of Tpn on the proliferation, invasion, apoptosis, and autophagy of TNBC cell lines MDA-MB-231 and MDA-MB-453. Additionally, Western blot (WB) experiments were utilized to detect the impact of Tpn on the expression of proteins including Wnt 3a, β-catenin, Cle-Caspase-3, Cle-PARP, autophagy regulator Beclin-1, p62, and LC3 in MDA-MB-231 and MDA-MB-453 cells. Results Different concentrations of Tpn (10 nm/L, 20 nm/L, 40 nm/L) were able to inhibit the clone formation ability of MDA-MB-231 and MDA-MB-453 cell lines, with 48-hour inhibition rates of 39.67%, 60.33%, and 79.14% for MDA-MB-231, and 44.33%, 52.34%, and 77.67% for MDA-MB-453, respectively. Additionally, Tpn inhibited their invasive abilities, with 48-hour inhibition rates of 26.33%, 33.67%, and 45.67% for MDA-MB-231, and 9.33%, 15.34%, and 66.33% for MDA-MB-453, respectively. Tpn also induced apoptosis, with 48-hour apoptosis rates of 10.06%, 12.66%, and 18.76% for MDA-MB-231, and 8.70%, 15.09%, and 19.18% for MDA-MB-453, respectively.Molecular mechanism experiments showed that after Tpn treatment, the expression levels of proteins such as Wnt 3a, β-catenin, and p62 significantly decreased in MDA-MB-231 and MDA-MB-453 cells, while the expression levels of proteins such as Cle-Caspase-3, Cle-PARP, and Beclin-1, as well as the LC3 II/I ratio, significantly increased.Conclusion Tpn is capable of inhibiting the clone formation and invasive abilities of MDA-MB-231 and MDA-MB-453 cells, as well as inducing apoptosis and autophagy. This mechanism is likely achieved through the regulation of the Wnt/β-catenin signaling pathway. |
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