二甲双胍联合紫杉醇对人乳腺癌细胞增殖抑制作用及其机制-东南大学学报医学版

二甲双胍联合紫杉醇对人乳腺癌细胞增殖抑制作用及其机制

单位：1. 承德医学院附属医院肿瘤科, 河北承德 067000;
2. 承德市第三医院胸腹外科, 河北承德 067000

分类号：R737.9

出版年·卷·期（页码）：2019·38·第一期（93-97）

摘要：

目的：探讨二甲双胍联合紫杉醇对人乳腺癌细胞增殖抑制作用及其机制。方法：将人乳腺癌细胞MCF-7分为对照组、二甲双胍组、紫杉醇组、二甲双胍组+紫杉醇联合组，MTT法检测各组人乳腺癌细胞MCF-7活力，实时荧光定量逆转录法测定miR-34a的表达水平，酶联免疫吸附法测定Ki-67、cyc D1、β-catenin、VEGF蛋白水平。结果：（1）二甲双胍组、紫杉醇组、联合组的OD值、存活率均低于对照组（P<0.05）；联合组OD值、存活率低于二甲双胍组、紫杉醇组（P<0.05）；二甲双胍组OD值、存活率与紫杉醇组比较无明显差异（P>0.05）；（2）二甲双胍组、紫杉醇组、联合组miR-34a表达水平均高于对照组（P<0.05）；联合组miR-34a表达水平高于二甲双胍组、紫杉醇组（P<0.05）；二甲双胍组miR-34a表达水平与紫杉醇组比较无明显差异（P>0.05）；（3）二甲双胍组、紫杉醇组、联合组Ki-67、cyc D1、β-catenin、VEGF蛋白水平均低于对照组（P<0.05）；联合组Ki-67、cyc D1、β-catenin、VEGF蛋白水平低于二甲双胍组、紫杉醇组（P<0.05）；二甲双胍组Ki-67、cyc D1、β-catenin、VEGF蛋白水平与紫杉醇组比较无明显差异（P>0.05）；miR-34a表达水平与存活率、Ki-67、cyc D1、β-catenin、VEGF蛋白呈明显负相关关系（P<0.05）。结论：二甲双胍与紫杉醇组联合作用能明显抑制人乳腺癌细胞MCF-7的增殖和转移，其机制与miR-34a介导抑制细胞周期、Wnt-β-catenin信号通路、VEGF有关。

Objective:To investigate the inhibitory effect of metformin combined with paclitaxel on human breast cancer cell proliferation and its mechanism. Methods:Human breast cancer cells MCF-7 were divided into three groups:control group, metformin group, paclitaxel group, combined group. MCF-7 activity of human breast cancer cells were detected by MTT assay, and the expression of miR-34a was measured by real-time fluorescence quantitative reverse transcriptase assay. The level of Ki-67,cyc D 1, β-catenin,VEGF, protein was determined by enzyme linked immunosorbent assay (ELISA). Results:(1) The OD and survival rate of the metformin group, the paclitaxel group and the combination group were significantly lower than those of the control group (t=10.46, 13.76, 12.15, 10.48, 13.14, 13.33, P<0.05). The OD value and survival rate of the combined group were significantly lower than those of the metformin group and the paclitaxel group (P<0.05). The OD value and survival rate in metformin group were similar to those in the paclitaxel group, and there was no significant difference between them (t=1.13,0.98, P>0.05). (2) The expression of miR-34a in the metformin group, the paclitaxel group and the combination group was significantly higher than that in the control group (P<0.05). The expression of miR-34a in the combination group was higher than that in the metformin group and the paclitaxel group (P<0.05). The expression of miR-34a in the metformin group was similar to that in the paclitaxel group (t=1.16,P>0 05). (3) the protein levels of Ki-67,cyc D1 and β-catenin,VEGF in the metformin group, the paclitaxel group and the combination group were significantly lower than those in the control group(P<0.05); The protein levels of Ki-67,cyc D1 and β-catenin,VEGF in the combined group were significantly lower than those in the the metformin group and the paclitaxel group (P<0.05). The levels of Ki-67,cyc D 1, β-catenin,VEGF protein in the metformin group were similar to those in the paclitaxel group, and there was no significant difference between them. The expression level of miR-34a was negatively correlated with survival rate, Ki-67,cyc D1, β-catenin,VEGF protein, and the difference was statistically significant (P<0.05). Conclusion:The combination of metformin and paclitaxel can significantly inhibit the proliferation and metastasis of MCF-7 cells. The mechanism is related to the inhibition of cell cycle, Wnt-β-catenin signaling pathway and VEGF by miR-34a.

参考文献：

[1] 董爱萍,韩良浩.乳腺癌患者生活质量测评量表及其应用[J].肿瘤,2017,37(1):107-116.
[2] 王乐,岳馨培,石菊芳,等.我国既往二十年乳腺癌经济负担研究[J].中国慢性病预防与控制,2017,25(2):143-146.
[3] 战祥毅,隋鑫,王文萍.中医治疗乳腺癌术后上肢淋巴水肿研究进展[J].临床军医杂志,2017,45(2):216-220.
[4] 陈峙霖,周恩相.保乳手术后乳腺癌患者血CD19⁺、自然杀伤细胞、白细胞介素-6水平变化及其对乳腺癌复发的预测价值[J].中国临床医生杂志,2017,45(1):63-65.
[5] 王晶晶,彭博,贺蓉,等.筋骨草和茯苓配伍合用抑制乳腺癌细胞侵袭转移作用及初步机制研究[J].中国药理学通报,2017,33(4):581-588.
[6] 国瑞琪,王秋红,王向涛,等.和厚朴酚脂质体的制备及其体内外抗乳腺癌作用研究[J].药物评价研究,2017,40(1):48-53.
[7] 高燕,徐桂芬,张华.二甲双胍相关性自噬与肿瘤的关系[J].现代肿瘤医学,2017,25(6):985-987.
[8] 霍小蕾,韩玲娜,裴振,等.香菇多糖联合紫杉醇对食管癌细胞生物学行为的影响[J].东南大学学报:医学版,2017,36(6):897-900.
[9] WANG D,CAO Q,QU M,et al.MicroRNA-616 promotes the growth and metastasis of non-small cell lung cancer by targeting SOX7[J].Oncol Rep,2017,38(4):2078-2079.
[10] BEG M S,BRENNER A J,SACHDEV J,et al.Phase I study of MRX34,a liposomal miR-34a mimic,administered twice weekly in patients with advanced solid tumors[J].Invest New Drugs,2017,35(2):180-181.
[11] 王晨飞,胡浩霖,吕建鑫,et al.乳腺癌侵袭相关分子的研究热点[J].东南大学学报:医学版,2018,37(4):734-738.
[12] QI H,LIU Z,LIU B,et al.micro-RNA screening and prediction model construction for diagnosis of salt-sensitive essential hypertension[J].Medicine,2017,96(17):6417-6419.
[13] 张展,徐娜,李爱萍,等.MiR-34a对JAR细胞自噬影响的机制[J].山东医药,2017,57(9):42-44.
[14] BEZAWY R E,CESARE M D,PENNATI M,et al.Antitumor activity of miR-34a in peritoneal mesothelioma relies on c-MET and AXL inhibition:persistent activation of ERK and AKT signaling as a possible cytoprotective mechanism[J].J Hematol Oncol,2017,10(1):19-21.
[15] 张金秋,朱萍,陆敏华,等.细胞免疫化学p16/Ki-67双染结合DNA倍体分析预测HSIL的研究[J].重庆医学,2017,46(13):1770-1772.
[16] Yang T W,GAO Y H,MA S Y,et al.Low-grade slightly elevated and polypoid colorectal adenomas display differential β-catenin-TCF/LEF activity,c-Myc,and cyclin D1 expression[J].World J Gastroenterol,2017,23(17):3066-3076.
[17] 李洪涛,刘昊,杨方军,等.电针对膝关节骨性关节炎大鼠关节软骨中Wnt3a、β-catenin蛋白表达的影响[J].针灸临床杂志,2017,33(3):65-68.
[18] JIANG C,ZUO F,WANG Y,et al.Progesterone changes VEGF and BDNF expression and promotes neurogenesis after ischemic stroke[J].Mol Neurobiol,2017,54(1):571-581.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录