沉默PI3K基因对E_2刺激后子宫内膜癌细胞增殖和凋亡的影响Effect of silencing PI3K gene on proliferation and apoptosis of endometrial cancer cells stimulated by E_2
陈坤;张洁清;李力;
摘要(Abstract):
目的:探讨沉默PI3K基因对雌激素刺激下的子宫内膜癌细胞增殖、迁移、凋亡的影响。方法:培养子宫内膜癌Ishikawa细胞,构建LV-PI3K-RNAi慢病毒载体转染Ishikawa细胞。实验分组:Control组:未经任何处理的Ishikawa细胞;Ishikawa组:经E_2刺激的Ishikawa细胞;NC组:经E_2刺激并转染阴性对照慢病毒的Ishikawa细胞;PI3Ki组:经E_2刺激并转染LV-PI3K-RNAi慢病毒的Ishikawa细胞。Real-time PCR、Western blot法检测各组VEGF、bFGF、PI3K mRNA及蛋白表达水平,MTT法、流式细胞仪分别检测细胞增殖能力及凋亡的情况。结果:与Ishikawa组、NC组比较,PI3Ki组的VEGF、bFGF、PI3K mRNA及蛋白表达水平明显降低,细胞增殖能力显著降低,凋亡率增高,差异均有统计学意义(P<0.05)。结论:PI3K基因低表达可干扰E_2在基因、蛋白水平激活Ishikawa细胞产生VEGF、bFGF,从而下调E_2对子宫内膜癌细胞增殖和抑制凋亡的影响。
关键词(KeyWords): 子宫内膜癌;雌二醇;VEGF;bFGF;RNA干扰;PI3K/Akt
基金项目(Foundation): 国家自然科学基金资助项目(No:81160318);; 广西自然科学基金资助项目(No:2013GXNSFAA019219)
作者(Authors): 陈坤;张洁清;李力;
DOI: 10.13283/j.cnki.xdfckjz.2021.04.006
参考文献(References):
- [1] Fujimoto J,Sakaguchi H,Hirose R,et al.Progestins suppress estrogen-induced expression of vascular endothelial growth factor (VEGF) subtypes in uterine endometrial cancer cells[J].Cancer Lett,1999,141(1-2):63-71
- [2] Pavlidou A,Vlahos NF.Molecular alterations of PI3K/Akt/mTOR pathway:a therapeutic target in endometrial cancer[J].Sci World J,2014,21(10):452-460
- [3] Yeramian A,Moreno-Bueno G,Dolcet X,et al.Endometrial carcinoma:molecular alterations involved in tumor development and progression[J].Oncogene,2013,32(4):403-413
- [4] 陆媛媛,张洁清,李力,等.雌激素通过激活AKT通路产生的细胞因子增强子宫内膜癌细胞增殖能力[J].中国癌症杂志,2014,23(11):868-873
- [5] 车晓霞,姜洁.PI3K/Akt/mTOR信号通路靶向治疗在子宫内膜癌中的研究进展[J].现代妇产科进展,2016,25(1):74-77
- [6] Guo RX,Wei LH,Tu Z,et al.17β-Estradiol activates PI3K/Akt signaling pathway by estrogen receptor (ER)-dependent and ER-independent mechanisms in endometrial cancer cells[J].J Steroid Biochem Mol Biol,2006,99(1):9-18
- [7] Gu C,Zhang ZB,Yu YH,et al.Inhibiting the PI3K/Akt pathway reversed progestin resistance in endometrial cancer[J].Cancer Sci,2011,102(3):557-564
- [8] Kim KJ,Li B,Winer J,et al.Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo[J].Nature,1993,362(6423):841-844
- [9] 宋红林,梁少凤,张洁清,等.雌二醇经丝苏氨酸蛋白激酶激活核因子κB通路对子宫内膜癌Ishikawa细胞增殖迁移的影响[J].中华肿瘤杂志,2014,36(11):811-815