冬凌草甲素诱导结直肠癌细胞SW-1116凋亡与衰老的体内外实验研究

Oridonin induces apoptosis and senescence of colorectal cancer SW1116 cells in vitro and in vivo

目的探讨冬凌草甲素(Ori)在体内外抑制结直肠癌细胞的作用及机制。方法应用不同浓度Ori(0、6.25、12.5、25、50和100μmol/L)处理结直肠癌细胞SW-1116及其建立的裸鼠移植瘤模型,CCK-8法检测Ori对SW-1116细胞的抗增殖效应;流式细胞仪检测Ori处理SW-1116后细胞周期的改变及细胞的凋亡;β-半乳糖苷酶染色检测Ori诱导SW-1116细胞衰老;软琼脂细胞克隆形成实验检测Ori对SW-1116细胞克隆形成的影响;观察Ori对SW-1116细胞裸鼠移植瘤生长的影响及其机制。结果 Ori可诱导结直肠癌细胞SW-1116生长抑制、细胞周期阻滞、凋亡、衰老和克隆形成能力。Ori还显著抑制SW-1116裸鼠移植瘤的生长,随着Ori剂量的增加裸鼠移植瘤中的细胞凋亡与衰老增加。结论体内外实验研究表明,Ori具有抗结直肠癌的活性,可能成为治疗结直肠癌的一个新的候选化合物。

Objective To explore the in vitro and in vivo antitumor effects of oridonin（Ori） on colorectal cancer and the related mechanisms.MethodsColorectal cancer cell line SW-1116 and established Xenograft models in nude mice were treated with different concentrations of Ori（0,6.25,12.5,25,50 and 100 μmol/L）.The antiproliferative effect of Ori on SW-1116 cells was assessed using CCK-8,the changes of cell cycle and cell apoptosis after treatment of SW-1116 cells with Ori were evaluated with flow cytometry,the senescence-associated expression of β-galactosidase activity was detected with a senescence detection kit,the effect of Ori on colony formation of SW-1116 cells was determined by soft agar cell clone formation test,and the effect and mechanism of Ori on the growth of Xenografts in nude mice were observed.ResultsOri induced growth inhibition,cell cycle arrest,apoptosis,senescence and suppressed colony-forming efficiency in colorectal cancer SW-1116 cells.Ori also significantly inhibited the in vivo growth of SW1116 cells in xenografts in nude mice,and the apoptosis and senescence increased with Ori dosage.ConclusionOri possesses in vitro and in vivo anti-colorectal cancer activities,and may represent a novel therapeutic option in treatment of colorectal cancer.