【摘要】 目的：探讨重金属锑对子宫内膜癌细胞增殖的影响，并揭示其促瘤调控机制。方法：将子宫内膜癌细胞AN3CA分为空白对照（Cont.）组、酒石酸钾（PTH）组和酒石酸锑钾（PAT）组；采用MTT及Edu试验检测不同浓度的PAT处理后子宫内膜癌细胞AN3CA的增殖能力；划痕实验及Transwell检测揭示子宫内膜癌细胞AN3CA的侵袭、迁移能力；通过ELISA法检测子宫内膜癌细胞AN3CA内雌激素水平。通过免疫缺陷（BALB/c）的裸鼠动物模型检测重金属锑暴露对肿瘤细胞体内增殖效应的影响，Western印迹检测雌激素受体（ER）及其下游靶点的表达情况。结果：低剂量锑（PAT,0～20μmol/L）暴露可显著促进子宫内膜癌细胞AN3CA的增殖，其中4μmol/L PAT作用最强（t=26.30、4.89，均P<0.05）。低剂量锑暴露（4μmol/L）可显著增强AN3CA细胞的侵袭和迁移能力，使Transwell穿膜细胞数增加（F=34.46,P<0.05），划痕愈合率提升2.25倍（t=26.17,P<0.05）。机制研究表明，低剂量锑暴露并未改变细胞内雌激素水平，与Cont.组相比，PAT组ER蛋白表达水平上调（F=1 081,P<0.000 1），同时，磷酸化磷脂酰肌醇3激酶（PI3K,F=1 308,P<0.000 1）、磷酸化蛋白激酶B(Akt,F=316.6,P<0.000 1)、磷酸化哺乳动物雷帕霉素靶蛋白（mTOR,F=4 184,P<0.000 1）表达升高。PAT暴露组肿瘤体积增长速率显著高于Cont.组及PTH暴露组（F=42.14,P<0.05）。结论：低剂量锑暴露通过类似雌激素效应，促进子宫内膜癌细胞的增殖及侵袭能力。更多还原

【Abstract】 Objective:To investigate the impact of the heavy metal antimony on the proliferation of endometrial cancer cells and elucidate its pro-tumor regulatory mechanisms. Methods:Endometrial cancer cells(AN3 CA) were divided into three groups:blank control(Cont.)group,potassium tartrate hemihydrate(PTH)exposure group,and potassium antimonyl tartrate(PAT)exposure group.Cell proliferation of endometrial cancer cells AN3 CA was assessed using MTT and Edu assays after treatment with varying concentrations of PAT. Scratch wound healing and Transwell assays were employed to evaluate the migratory and invasive capabilities of AN3 CA cells. The estrogen level in AN3 CA endometrial cancer cells was measured via ELISA. A BALB/c nude mouse model was used to examine the effects of heavy metal antimony exposure on tumor cells proliferation in vivo. Western blotting was performed to analyze the expression of estrogen receptor(ER) and its downstream targets. Results:Low-dose antimony exposure(as PAT,0-20 μmol/L)significantly promoted the proliferation of endometrial cancer cells AN3 CA,with the most potent effect observed at 4 μmol/L PAT(t=26.30,4.89,both P<0.05). Exposure to low-dose antimony(4 μmol/L)markedly enhanced the invasive and migratory capacities of AN3 CA cells,evidenced by increased Transwell cell penetration(t=6.89,P<0.05)and a 2.25-fold elevation in wound healing rate(t=26.17,P<0.05). Mechanistic investigations revealed that low-dose antimony exposure did not alter intracellular estrogen levels.Compared to the Cont. group,the PAT group showed upregulation of ER protein expression(F=1 081,P<0.000 1),meanwhile,the levels of phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)(F=1 308,P<0.0001),phospho-protein kinase B(Akt,F=316.6,P<0.000 1),and phospho-mammalian target of rapamycin(mTOR,F=4 184,P<0.000 1)were significantly elevated. The tumor volume growth rate in the PAT exposure group was significantly higher than that in the Cont. group and the PTH exposure group(F=42.14,P<0.05). Conclusion:Low-dose antimony exposure promotes the proliferation and invasion of endometrial cancer cells via estrogenlike effects.更多还原