二甲双胍增加他莫昔芬对MCF-7细胞敏感性相关机制的探讨
发布时间：2019-06-05 22:03
【摘要】：目的： 研究他莫西芬联合二甲双胍对乳腺癌细胞MCF-7的影响，并探讨二甲双胍与他莫昔芬联合应用对肿瘤抑制作用的相关机制进行研究。 材料与方法： 1.采用MTT法检测不同浓度二甲双胍及二甲双胍联合他莫西芬对MCF-7细胞的抑制作用，并测量第24、48、72小时的OD值，计算各组的抑制率； 2.采用Western blot技术检测细胞内蛋白质表达状况，采用Real time PCR技术检测细胞内mRNA水平； 3.进行划痕实验观察细胞的迁移能力。 结果： MTT结果显示，，二甲双胍对MCF-7细胞具有抑制作用，随着二甲双胍浓度的增加及作用时间的延长，抑制效果越明显，各组间结果具有显著的差异性（p＜0.05）。研究结果还发现二甲双胍与他莫昔芬联合应用时较单独应用二甲双胍的抑制效果明显（p＜0.05），且呈剂量依赖性。Western Blot及RT-PCR结果显示：二甲双胍及（或）他莫昔芬处理48小时后，HIF-1α-1、mTOR、Vimentin3种蛋白及mRNA的表达水平均有下降，随着二甲双胍的剂量增加其表达下降，这种现象在联合应用组更为明显，差异具有统计学意义。划痕实验结果显示，二甲双胍对肿瘤细胞的愈合有抑制作用，两者联合应用可以抑制肿瘤细胞的迁移能力。 结论： 1.二甲双胍对MCF-7细胞具有抑制作用，且这种作用随着浓度及时间的增加，效果越明显； 2.联合应用二甲双胍与他莫昔芬对肿瘤细胞的抑制作用较单独应用时显著； 3.二甲双胍可能对mTOR、HIF-1α、波性蛋白等相关癌基因进行抑制，从而降低乳腺癌MCF-7细胞的恶性行为； 4.二甲双胍增加他莫昔芬的敏感性，提高内分泌治疗的效果，起到增敏的作用。
[Abstract]:Aim: to study the effect of tamoxifen combined with metformin on breast cancer cell line MCF-7 and to explore the mechanism of combination of metformin and tamoxifen on tumor inhibition. Materials and methods: 1. MTT assay was used to detect the inhibitory effect of different concentrations of metformin and metformin combined with tamoxifen on MCF-7 cells, and the ODvalues of 24, 48 and 72 hours were measured, and the inhibition rates of each group were calculated. 2. Western blot technique was used to detect the expression of protein in cells, and Real time PCR technique was used to detect the level of mRNA in cells. The migration ability of cells was observed by scratch test. Results: the results of MTT showed that metformin had inhibitory effect on MCF-7 cells. With the increase of metformin concentration and the prolongation of action time, the inhibitory effect was more obvious, and there was significant difference among the three groups (p < 0.05). The results also found that the inhibitory effect of metformin combined with tamoxifen was more obvious than that of metformin alone (p < 0.05). The results of Western Blot and RT-PCR showed that after 48 hours of metformin and / or tamoxifen treatment, the expression levels of HIF-1 伪-1, mTor, Vimentin and mRNA decreased. With the increase of metformin dose, the expression of metformin decreased, which was more obvious in the combined application group, and the difference was statistically significant. The results of scratch test showed that metformin could inhibit the healing of tumor cells, and the combination of metformin and metformin could inhibit the migration of tumor cells. Conclusion: 1. Metformin has inhibitory effect on MCF-7 cells, and the effect is more obvious with the increase of concentration and time. The inhibitory effect of metformin and tamoxifen on tumor cells was more significant than that of metformin alone. Metformin may inhibit mTOR,HIF-1 伪, wavy protein and other related Oncogenes, thus reducing the malignant behavior of breast cancer MCF-7 cells. 4. Metformin increases the sensitivity of tamoxifen, improves the effect of endocrine therapy, and increases the sensitivity of tamoxifen.
【学位授予单位】：辽宁中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R96
本文编号：2493854
[Abstract]:Aim: to study the effect of tamoxifen combined with metformin on breast cancer cell line MCF-7 and to explore the mechanism of combination of metformin and tamoxifen on tumor inhibition. Materials and methods: 1. MTT assay was used to detect the inhibitory effect of different concentrations of metformin and metformin combined with tamoxifen on MCF-7 cells, and the ODvalues of 24, 48 and 72 hours were measured, and the inhibition rates of each group were calculated. 2. Western blot technique was used to detect the expression of protein in cells, and Real time PCR technique was used to detect the level of mRNA in cells. The migration ability of cells was observed by scratch test. Results: the results of MTT showed that metformin had inhibitory effect on MCF-7 cells. With the increase of metformin concentration and the prolongation of action time, the inhibitory effect was more obvious, and there was significant difference among the three groups (p < 0.05). The results also found that the inhibitory effect of metformin combined with tamoxifen was more obvious than that of metformin alone (p < 0.05). The results of Western Blot and RT-PCR showed that after 48 hours of metformin and / or tamoxifen treatment, the expression levels of HIF-1 伪-1, mTor, Vimentin and mRNA decreased. With the increase of metformin dose, the expression of metformin decreased, which was more obvious in the combined application group, and the difference was statistically significant. The results of scratch test showed that metformin could inhibit the healing of tumor cells, and the combination of metformin and metformin could inhibit the migration of tumor cells. Conclusion: 1. Metformin has inhibitory effect on MCF-7 cells, and the effect is more obvious with the increase of concentration and time. The inhibitory effect of metformin and tamoxifen on tumor cells was more significant than that of metformin alone. Metformin may inhibit mTOR,HIF-1 伪, wavy protein and other related Oncogenes, thus reducing the malignant behavior of breast cancer MCF-7 cells. 4. Metformin increases the sensitivity of tamoxifen, improves the effect of endocrine therapy, and increases the sensitivity of tamoxifen.
【学位授予单位】：辽宁中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R96
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本文编号：2493854
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