【摘要】：目的： 研究他莫西芬聯(lián)合二甲雙胍對乳腺癌細胞MCF-7的影響，并探討二甲雙胍與他莫昔芬聯(lián)合應用對腫瘤抑制作用的相關(guān)機制進行研究。 材料與方法： 1.采用MTT法檢測不同濃度二甲雙胍及二甲雙胍聯(lián)合他莫西芬對MCF-7細胞的抑制作用，并測量第24、48、72小時的OD值，計算各組的抑制率； 2.采用Western blot技術(shù)檢測細胞內(nèi)蛋白質(zhì)表達狀況，采用Real time PCR技術(shù)檢測細胞內(nèi)mRNA水平； 3.進行劃痕實驗觀察細胞的遷移能力。 結(jié)果： MTT結(jié)果顯示，，二甲雙胍對MCF-7細胞具有抑制作用，隨著二甲雙胍濃度的增加及作用時間的延長，抑制效果越明顯，各組間結(jié)果具有顯著的差異性（p＜0.05）。研究結(jié)果還發(fā)現(xiàn)二甲雙胍與他莫昔芬聯(lián)合應用時較單獨應用二甲雙胍的抑制效果明顯（p＜0.05），且呈劑量依賴性。Western Blot及RT-PCR結(jié)果顯示：二甲雙胍及（或）他莫昔芬處理48小時后，HIF-1α-1、mTOR、Vimentin3種蛋白及mRNA的表達水平均有下降，隨著二甲雙胍的劑量增加其表達下降，這種現(xiàn)象在聯(lián)合應用組更為明顯，差異具有統(tǒng)計學意義。劃痕實驗結(jié)果顯示，二甲雙胍對腫瘤細胞的愈合有抑制作用，兩者聯(lián)合應用可以抑制腫瘤細胞的遷移能力。 結(jié)論： 1.二甲雙胍對MCF-7細胞具有抑制作用，且這種作用隨著濃度及時間的增加，效果越明顯； 2.聯(lián)合應用二甲雙胍與他莫昔芬對腫瘤細胞的抑制作用較單獨應用時顯著； 3.二甲雙胍可能對mTOR、HIF-1α、波性蛋白等相關(guān)癌基因進行抑制，從而降低乳腺癌MCF-7細胞的惡性行為； 4.二甲雙胍增加他莫昔芬的敏感性，提高內(nèi)分泌治療的效果，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 偽-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 偽, 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.
【學位授予單位】：遼寧中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R96

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