[1]张铮铮,刘 筱,徐 浩,等.骨化三醇、雷帕霉素及其联合使用对人子宫内膜癌Ishikawa细胞株的作用及机制研究[J].中国药理学通报,2018,(10):1444-1449.[doi:10.3969/j.issn.1001-1978.2018.10.023]
 ZHANG Zheng-zheng,LIU Xiao,XU Hao,et al.Effect of calcitriol, rapamycin and their combination on human endometrial carcinoma Ishikawa cells in vitro and its mechanism[J].Chinese Pharmacological Bulletin,2018,(10):1444-1449.[doi:10.3969/j.issn.1001-1978.2018.10.023]
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骨化三醇、雷帕霉素及其联合使用对人子宫内膜癌Ishikawa细胞株的作用及机制研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年10期
页码:
1444-1449
栏目:
论著
出版日期:
2018-09-26

文章信息/Info

Title:
Effect of calcitriol, rapamycin and their combination on human endometrial carcinoma Ishikawa cells in vitro and its mechanism
文章编号:
1001-1978(2018)10-1444-06
作者:
张铮铮12刘 筱3徐 浩12魏 敏12杜文升12陆晓媛12
徐州医科大学 1.附属医院妇产科、2.妇产科教研室、3.附属医院急救中心,江苏 徐州 221002
Author(s):
ZHANG Zheng-zheng12 LIU Xiao3 XU Hao12 WEI Min12 DU Wen-sheng12 LU Xiao-yuan12
1.Dep of Gynaecology and Obstetrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou Jiangsu 221002, China; 2.Teaching and Research of Gynaecology and Obstetrics, Xuzhou Medical University, Xuzhou Jiangsu 221002, China; 3.Dept of Emergency Center, Affiliated Hospital of Xuzhou Medical University, Xuzhou Jiangsu 221002, China
关键词:
骨化三醇 雷帕霉素 增殖 信号通路 Akt-mTOR 子宫内膜癌
Keywords:
calcitriol: rapamycin cell proliferation signaling pathway Akt-mTOR endometrial carcinoma
分类号:
R329.24; R329.28; R737.330.22; R979.1
DOI:
10.3969/j.issn.1001-1978.2018.10.023
文献标志码:
A
摘要:
目的 观察骨化三醇、雷帕霉素及其联合使用对人子宫内膜癌Ishikawa细胞抑癌作用及其可能的作用机制。方法 采用MTT法检测不同浓度的骨化三醇、雷帕霉素对人子宫内膜癌细胞株Ishikawa抑制率的影响; 用倒置显微镜观察细胞形态学改变; 流式细胞仪检测细胞增殖周期的变化; RT-PCR检测Akt、mTOR mRNA的表达; Western blot检测Akt、mTOR蛋白的表达。结果 10-7 mol·L-1骨化三醇组和50.0 nmol·L-1的雷帕霉素与人子宫内膜癌Ishikawa细胞株共培养48 h为二者抑癌效应适宜浓度和时间点。联合用药组对细胞的增殖抑制率均高于单独应用骨化三醇、雷帕霉素组,而Akt/mTOR信号物质表达量均明显降低(P<0.05)。结论 骨化三醇联合雷帕霉素可协同抑制人子宫内膜癌细胞株Ishikawa的增殖,其机制可能是通过抑制PI3K/Akt/mTOR信号通路,从而发挥抑制子宫内膜癌增殖的作用。
Abstract:
Aim To explore the effect of calcitriol, rapamycin and their combination administeredd to the human endometrial carcinoma Ishikawa cells and the underlying mechanism.Methods The growth inhibition ratio of the human endometrial carcinoma Ishikawa cells administered by calcitriol, rapamycin and their combination in vitro was observed by MTT.The morphological changes of the cells were observed using phase-contrast microscopy.The proliferation cycle was detected with flow cytometry.The expressions of Akt and mTOR mRNA and protein were assessed by RT-PCR and Western blot, respectively.Results It was a suitable concentration and time point of 10-7 mol·L-1 calcitriol, 50.0 nmol·L-1 rapamycin and human endometrial carcinoma Ishikawa cells co-culture about 48 h.The inhibitory rate of the combination group was higher than that of the calcitriol and rapamycin group(P<0.05).However, the expressions of Akt and mTOR mRNA and proteins of the combination group were significantly lower than those of the calcitriol and rapamycin group alone(P<0.05).Conclusions The calcitriol, rapamycin and their combination with appropriate concentration and time may inhibit Ishikawa cell growth significantly, but the effect of their combination is better than that of the calcitriol and rapamycin alone.The mechanism may be related to the inhibition of the signaling pathway of PI3K/Akt/mTOR.

参考文献/References:

[1] Pautier P, Pommeret F.Systemic therapy for advanced endometrial cancer[J].Bull Cancer, 2017, 104(12):1046-53.
[2] Ethier J L, Desautels D N, Amir E, et al.Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis[J].Gynecol Oncol, 2017,147(1):158-66.
[3] Rohira A D, Lonard D M.Steroid receptor coactivators present a unique opportunity for drug development in hormone-dependent cancers[J].Biochem Pharmacol, 2017, 140:1-7.
[4] Gupta A, Kaur C D, Saraf S, Saraf S.Targeting of herbal bioactives through folate receptors: a novel concept to enhance intracellular drug delivery in cancer therapy[J].J Recept Signal Transduct Res, 2017,37(3):314-23.
[5] 陈景锋,罗世英,崔 燎.丹参素对糖皮质激素诱导骨丢失大鼠胫骨近端骨密度和骨微结构的影响[J].中国药理学通报,2015,31(12):1681-7.
[5] Chen J F,Luo S Y, Cui L.Effect of tanshinol on bone mineral density and microstructure of proximal tibias in rats with bone loss induced by glucocorticoid[J].Chin Pharmacol Bull, 2015,31(12):1681-7.
[6] 许成芳,李小毛,李 田,王小韵.紫杉醇对PTEN不同状态的子宫内膜癌细胞株的作用及其机制探讨[J].中国药理学通报, 2011,27(11):1528-32.
[6] Xu C F, Li X M, Li T, Wang X Y.The effect of taxol on endometrial cancer cells with different PTEN status[J].Chin Pharmacol Bull, 2011, 27(11):1528-32.
[7] Grabiner B C, Nardi V, Birsoy K, et al.A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity[J].Cancer Discov, 2014,4(5):554-63.
[8] 张铮铮,陆晓媛,张励才.经牵涉区皮下局麻药抑制大鼠子宫炎性痛的实验研究[J].中国药理学通报,2014,30(1):131-4.
[8] Zhang Z Z, Lu X Y, Zhang L C.Experimental study on analgesia with local anesthetic via referred area of rat metralgia[J].Chin Pharmacol Bull, 2014,30(1):131-4.
[9] Fang Y.Compound annotation with real time cellular activity profiles to improve drug discovery[J].Expert Opin Drug Discov, 2016,11(3):269-80.
[10] Matson J P, Cook J G.Cell cycle proliferation decisions: the impact of single cell analyses[J].FEBS J, 2017,284(3):362-75.
[11] 赵 爽,叶 强,李 涛,范忠才.炎症应激通过激活 mTOR通路诱导THP-1巨噬细胞泡沫化的实验研究[J].中国药理学通报, 2016,32(8):1105-10.
[11] Zhao S,Ye Q,Li T, Fan Z C.Experiment of THP-1 macrophage foam-cell formation through mTOR signal pathway activation induced by inflammatory strss[J].Chin Pharmacol Bull, 2016,32(8):1105-10.
[12] Bliskovsky V, Ramsay E S, Scott J, et al.Frap, FKBP12 rapamycin-associated protein, is a candidate gene for the plasmacytoma resistance locus Pctr2 and can act as a tumor suppressor gene[J].Proc Natl Acad Sci USA, 2003,100(25):14982-7.
[13] Dedes K J, Wetterskog D, Ashworth A, et al.Emerging therapeutic targets in endometrial cancer[J].Nat Rev Clin Oncol, 2011,8(5):261-71.
[14] Subramanian C, Grogan P T, Opipari V P, et al.Novel natural with anolides induce apoptosis and inhibit migration of neuroblastoma cells through down regulation of N-myc and suppression of Akt/mTOR/NF-κB activation[J].Oncotarget, 2018,9(18):14509-23.
[15] Lawrence J, Nho R.The role of the mammalian target of rapamycin(mTOR)in pulmonary fibrosis[J].Int J Mol Sci, 2018,19(3):1-31.

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备注/Memo

备注/Memo:
收稿日期:2018-06-20,修回日期:2018-07-24
基金项目:国家自然科学基金资助项目(No 81371243); 江苏省徐州市推动科技创新专项基金后补助备案项目(No KH17045)
作者简介:张铮铮(1983-),女,硕士生,主治医师,研究方向:妇科肿瘤的基础与临床,E-mail:105681672@qq.com;
陆晓媛(1968-),女,博士,主任医师,研究方向:妇科肿瘤的基础与临床,通讯作者,E-mail:18052268119@189.cn
更新日期/Last Update: 2018-08-26