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重楼皂苷Ⅸ通过调节Fas/FasL信号通路诱导肝癌细胞凋亡及对裸鼠移植瘤生长的抑制作用
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| 篇名： | 重楼皂苷Ⅸ通过调节Fas/FasL信号通路诱导肝癌细胞凋亡及对裸鼠移植瘤生长的抑制作用 |
| TITLE： | Induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 through regulating the Fas/FasL sig-naling pathway and the inhibitory effect on the growth of transplanted tumor in nude mice |
| 摘要： | 目的 探讨重楼皂苷Ⅸ通过调节凋亡相关因子Fas/Fas配体（FasL）信号通路对肝癌细胞凋亡的诱导作用以及其对裸鼠移植瘤生长的抑制作用。方法在细胞系及干预条件筛选的基础上，以HepG2细胞为对象，考察2、4μmol/LPP9干预对细胞克隆形成能力、凋亡率以及Fas、FasL、切割的胱天蛋白酶8（cleavedcaspase-8）、cleavedcaspase-3蛋白表达的影响；引入Fas抑制剂KR-33493，考察PP9抗肝癌活性的潜在机制。以HepG2细胞荷瘤裸鼠模型为对象，以5-氟尿嘧啶（20mg/kg）为阳性对照，考察10mg/kgPP9对荷瘤裸鼠瘤体体积、瘤体质量、细胞核增殖相关抗原Ki-67、cleavedcaspase-3蛋白表达的影响。结果与对照组比较，2、4μmol/LPP9可显著降低细胞的克隆数和克隆形成率，显著升高其凋亡率和Fas、FasL、cleavedcaspase-8、cleavedcaspase-3蛋白的表达水平（P＜0.05或P＜0.01）；而联用KR-33493可显著逆转PP9对Fas/FasL信号通路相关蛋白表达的上调作用（P＜0.01）。与对照组裸鼠比较，PP9组裸鼠的瘤体体积（第27天）、瘤体质量、Ki-67蛋白的表达水平均显著降低，cleavedcaspase-3蛋白的表达水平显著升高（P＜0.01）。结论PP9可通过激活Fas/FasL信号通路来诱导肝癌HepG2细胞凋亡；同时，PP9还能有效抑制裸鼠移植瘤的生长。 |
| ABSTRACT： | OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice. |
| 期刊： | 2025年第36卷第18期 |
| 作者： | 姚敏娜；张伟；高凯；李锐莉；殷英；郭超；陆云阳；汤海峰；王婧雯 |
| AUTHORS： | YAO Minna， ZHANG Wei，GAO Kai，LI Ruili，YIN Ying，GUO Chao，LU Yunyang，TANG Haifeng，WANG Jingwen |
| 关键字： | 重楼皂苷Ⅸ；肝细胞癌；HepG2细胞；凋亡；Fas/FasL信号通路 |
| KEYWORDS： | polyphyllin 9； hepatocellular carcinoma； |
| 阅读数： | 8 次 |
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