【摘要】：本研究首先以4株人源乳腺癌細(xì)胞MCF7、MDA-MB-231、MDA-MB-453和SK-BR-3為基礎(chǔ),通過大量MTT實(shí)驗確定鬼臼毒素作為典型的體外抗乳腺癌天然藥物。分析比較鬼臼毒素對各人源乳腺癌細(xì)胞的IC50值,確認(rèn)出對鬼臼毒素較為敏感細(xì)胞株MDA-MB-453和SK-BR-3。Hoechst染色法和流式細(xì)胞術(shù)檢測鬼臼毒素誘導(dǎo)高表達(dá)HER2陽性乳腺癌細(xì)胞凋亡的能力,Western blot和實(shí)時熒光定量PCR實(shí)驗分別檢測鬼臼毒素作用后高表達(dá)HER2陽性乳腺癌細(xì)胞中Cleaved-caspase-3、Cleaved-caspase-9、Bcl-2Bax等凋亡相關(guān)蛋白和mRNA的表達(dá)水平。結(jié)果顯示,相比5FU和大黃素,鬼臼毒素對多種人源乳腺癌細(xì)胞增殖的抑制作用更顯著(P0.05),可以作為典型的體外抗乳腺癌天然藥物。相比于HER2陰性乳腺癌細(xì)胞MCF7和MDA-MB-231,鬼臼毒素作用下高表達(dá)HER2陽性乳腺癌細(xì)胞MDA-MB-453和SK-BR-3都發(fā)生了明顯凋亡(P0.05);其機(jī)制可能是一方面通過激活Cleaved-caspase-3、Cleaved-caspase-9,另一方面通過上調(diào)Bax,下調(diào)Bcl-2激活線粒體途徑來誘導(dǎo)高表達(dá)HER2陽性乳腺癌細(xì)胞凋亡(P0.05)。
[Abstract]:In this study, based on four human breast cancer cell lines MCF7,MDA-MB-231,MDA-MB-453 and SK-BR-3, podophyllotoxin was identified as a typical natural anti-breast cancer drug by a large number of MTT experiments. The IC50 values of podophyllotoxin on human breast cancer cells were analyzed and compared. To confirm the ability of podophyllotoxin sensitive cell line MDA-MB-453 and SK-BR-3.Hoechst staining and flow cytometry to detect apoptosis induced by podophyllotoxin in high expression HER2 positive breast cancer cells. Western blot and real-time fluorescence quantitative PCR assay were used to detect the expression of Cleaved-caspase-3,Cleaved-caspase-9,Bcl-2Bax and mRNA in HER2 positive breast cancer cells after podophyllotoxin treatment. The results showed that podophyllotoxin could inhibit the proliferation of human breast cancer cells more significantly than 5FU and emodin (P0.05) and could be used as a typical anti-breast cancer natural drug in vitro. Compared with HER2 negative breast cancer cells MCF7 and MDA-MB-231, podophyllotoxin high expression of HER2 positive breast cancer cells MDA-MB-453 and SK-BR-3 were significantly apoptotic (P0.05). On the one hand, the mechanism may be by activating Cleaved-caspase-3,Cleaved-caspase-9, on the other hand, by up-regulating Bax, down-regulating Bcl-2 and activating mitochondrial pathway to induce apoptosis of high expression HER2 positive breast cancer cells (P0.05).
【學(xué)位授予單位】：華東理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9

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