双酚A激活PI3K/AKT通路促进子宫内膜癌细胞增殖的研究
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摘要
目的:研究双酚A(bisphenol A,BPA)活化磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)促子宫内膜癌细胞Ishikawa和RL952增殖的机制。方法:CCK8试剂盒检测Ishikawa和RL952细胞的增殖情况,蛋白质印迹(Western blotting)法检测p-AKT蛋白的表达。结果:在Ishikawa和RL952细胞中,BPA作用48 h时,细胞增殖呈浓度依赖性,1μmol/L的BPA促细胞生长效应最显著,Ishikawa和RL952细胞增殖率分别为0.758±0.023和0.692±0.042。BPA浓度超过1μmol/L后,促细胞增殖的作用下降。BPA作用24 h时促增殖效应不明显,BPA作用72 h时表现出细胞毒作用。1μmol/L BPA处理的Ishikawa和RL952细胞48 h后p-AKT蛋白的表达较对照组升高(P<0.05),加入PI3K抑制剂(LY294002),p-AKT的蛋白表达比对照组降低,但差异无统计学意义(P>0.05)。结论:BPA通过激活PI3K/AKT通路促进子宫内膜癌细胞增殖。
Objective:To explore the mechanism of bisphenol A on the proliferation in human endometrial cancer cells(Ishikawa and RL952) via PI3 K/AKT signaling pathway. Methods:CCK8 assay was used to detect the proliferation in Ishikawa and RL952 cells, and Western blotting was applied to observe the expression of phosphorylation-AKT. Results:Ishikawa and RL952 cells proliferation increased significantly with treatment of 1 μmol/L BPA after 48 h, and cell proliferation was(0.758±0.023) and(0.692±0.042) respectively(P<0.01). The proliferation effect decreased when BPA was more than 1 μmol/L. Ishikawa and RL952 cells did not increase after treated for 24 h. Cytotoxic effects were showed after BPA treated for 72 h. After 1 μmol/L BPA treated for48 h, p-AKT expression was increased significantly compared with controls(P<0.05). When PI3 K was blocked by LY294002, pAKT expression was decreased, but it is not significant compared to controls(P >0.05). Conclusions:Bisphenol A induced endometrial cancer cell proliferation by activating PI3 K/AKT pathway.
Objective:To explore the mechanism of bisphenol A on the proliferation in human endometrial cancer cells(Ishikawa and RL952) via PI3 K/AKT signaling pathway. Methods:CCK8 assay was used to detect the proliferation in Ishikawa and RL952 cells, and Western blotting was applied to observe the expression of phosphorylation-AKT. Results:Ishikawa and RL952 cells proliferation increased significantly with treatment of 1 μmol/L BPA after 48 h, and cell proliferation was(0.758±0.023) and(0.692±0.042) respectively(P<0.01). The proliferation effect decreased when BPA was more than 1 μmol/L. Ishikawa and RL952 cells did not increase after treated for 24 h. Cytotoxic effects were showed after BPA treated for 72 h. After 1 μmol/L BPA treated for48 h, p-AKT expression was increased significantly compared with controls(P<0.05). When PI3 K was blocked by LY294002, pAKT expression was decreased, but it is not significant compared to controls(P >0.05). Conclusions:Bisphenol A induced endometrial cancer cell proliferation by activating PI3 K/AKT pathway.
引文
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[12]徐彦楠,周晨明,姚胜杰,等.PI3K/Akt信号转导通路与肿瘤细胞增殖[J].河北医科大学学报,2015,36(1):107-109.
[2]Chen W,Zheng R,Baade PD,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[3]Morice P,Leary A,Creutzberg C,et al.Endometrial cancer[J].Lancet,2016,387(10023):1094-1108.
[4]Lee HS,Park EJ,Oh JH,et al.Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase activity[J].Biosci Biotechnol Biochem,2014,78(8):1371-1375.
[5]Bergeron RM,Thompson TB,Leonard LS,et al.Estrogenicity of bisphenol A in a human endometrial carcinoma cell line[J].Mol Cell Endocrinol,1999,150(1/2):179-187.
[6]Wang KH,Kao AP,Chang CC,et al.Bisphenol A-induced epithelial to mesenchymal transition is mediated by cyclooxygenase-2 upregulation in human endometrial carcinoma cells[J].Reprod Toxicol,2015,58:229-233.
[7]Tarapore P,Ying J,Ouyang B,et al.Exposure to bisphenol Acorrelates with early-onset prostate cancer and promotes centrosome amplification and anchorage-independent growth in vitro[J].PLoSOne,2014,9(3):e90332.
[8]Ma H,Yao Y,Wang C,et al.Transcription factor activity of estrogen receptorαactivation upon nonylphenol or bisphenol A treatment enhances the in vitro proliferation,invasion,and migration of neuroblastoma cells[J].Onco Targets Ther,2016,9:3451-3463.
[9]Trabert B,Falk RT,Figueroa JD,et al.Urinary bisphenol A-glucuronide and postmenopausal breast cancer in Poland[J].Cancer Causes Control,2014,25(12):1587-1593.
[10]Ptak A,Gregoraszczuk EL.Effects of bisphenol A and 17β-estradiol on vascular endothelial growth factor A and its receptor expression in the non-cancer and cancer ovarian cell lines[J].Cell Biol Toxicol,2015,31(3):187-197.
[11]Malloy KM,Wang J,Clark LH,et al.Novasoy and genistein inhibit endometrial cancer cell proliferation through disruption of the AKT/mTOR and MAPK signaling pathways[J].Am J Transl Res,2018,10(3):784-795.
[12]徐彦楠,周晨明,姚胜杰,等.PI3K/Akt信号转导通路与肿瘤细胞增殖[J].河北医科大学学报,2015,36(1):107-109.