本文選題：小檗堿 + 乳腺癌　； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景乳腺癌是一種女性常見的惡性腫瘤,嚴(yán)重影響身心健康甚至危害生命,其在女性癌癥發(fā)病率中位居第一。乳腺癌的治療主要以手術(shù)為主,并且配合術(shù)后化療、靶向治療等綜合療法,但放、化療過程中的不良反應(yīng)以及多藥物耐藥現(xiàn)象所導(dǎo)致的治療失敗仍是臨床需進(jìn)一步解決的問題。因此,尋找有效、低毒、天然、副作用小的中藥治療乳腺癌及其相關(guān)的研究已成為一個緊迫的問題。小檗堿又名黃連素,是一種常見的異喹啉類生物堿,從黃蓮、黃柏等中草藥中提取獲得,具有抗病原微生物和抗菌的功效。小檗堿可以通過促進(jìn)腫瘤細(xì)胞凋亡、抑制腫瘤細(xì)胞增殖、抑制腫瘤細(xì)胞轉(zhuǎn)移以及增強(qiáng)腫瘤細(xì)胞對化療藥物的敏感性等方式起一定的抗腫瘤作用。小檗堿與乳腺癌之間的關(guān)系是目前的研究熱點,體內(nèi)研究尚未見報道。因此,本課題希望通過將人乳腺癌細(xì)胞MCF-7接種于裸鼠皮下,建立裸鼠乳腺癌動物模型,研究鹽酸小檗堿對MCF-7乳腺癌小鼠體內(nèi)產(chǎn)生的作用與影響。目的本課題通過將人乳腺癌細(xì)胞系MCF-7接種于裸鼠背部皮下,建立乳腺癌動物模型,研究鹽酸小檗堿對MCF-7乳腺癌小鼠體內(nèi)產(chǎn)生的作用與影響。方法一、在小鼠右背部皮下接種細(xì)胞,建立人乳腺癌MCF-7移植瘤裸鼠模型,計算出藥物的抑瘤療效(TGI)。二、應(yīng)用HE染色法檢測各實驗組的裸鼠移植瘤組織的染色情況。三、應(yīng)用TUNEL染色法檢測各實驗組的裸鼠移植瘤組織的細(xì)胞凋亡情況。四、應(yīng)用流式細(xì)胞儀檢測各實驗組的裸鼠移植瘤組織的細(xì)胞周期情況。五、應(yīng)用免疫組化SP法、Western blot檢測各實驗組的裸鼠移植瘤組織的MMP-2、MMP-9、p53、EGFR蛋白的表達(dá)情況。結(jié)果1、裸鼠移植瘤生長情況:(1)每組大鼠在第21天時的體重均比第1天有所下降,各組具有統(tǒng)計學(xué)差異(P0.05)。(2)五組裸鼠的體積差異有統(tǒng)計學(xué)意義(P0.05)。2、各藥物組的腫瘤抑制率:B1、B2、B3、C組的TGI值分別是5.55%、4.91%、58.88%、67.72%,差異均有顯著性差異(P0.01)。3、裸鼠移植瘤組織病理學(xué)變化:(1)肉眼:移植瘤呈圓形、類圓形或分葉狀生長。(2)光鏡:腫瘤細(xì)胞略增大,治療組異型細(xì)胞減少,瘤組織結(jié)構(gòu)破壞。4、TUNEL染色結(jié)果顯示:各組間細(xì)胞凋亡指數(shù)比較有統(tǒng)計學(xué)差異(p0.01)。5、流式細(xì)胞術(shù)結(jié)果顯示:(1)S期所占細(xì)胞周期分布經(jīng)方差分析顯示:各組間比較均有顯著性差異(P0.01);(2)Go/G1期所占細(xì)胞周期分布經(jīng)方差分析顯示:各組間比較均有顯著性差異(P0.01)。6、免疫組化、Western blot結(jié)果顯示:MMP-2、MMP-9、P53、EGFR蛋白在對照組中的表達(dá)量顯著高于其他實驗組,其組間差異有統(tǒng)計學(xué)意義(P0.05)。結(jié)論1.成功建立了裸鼠人乳腺癌MCF-7細(xì)胞皮下移植瘤疾病模型。2.小檗堿能夠抑制MCF-7乳腺癌裸鼠腫瘤生長,抑制作用呈濃度依賴性。
[Abstract]:Background breast cancer is a common malignant tumor in women, which seriously affects physical and mental health and even endangers life. It ranks first in the incidence of female cancer. The treatment of breast cancer is mainly based on surgery, combined with postoperative chemotherapy, targeted therapy and other comprehensive therapies, but the adverse reactions in the process of chemotherapy and the phenomenon of multi drug resistance are in the process of chemotherapy. Therefore, it has become an urgent problem to find effective, low toxic, natural, and minor side effects in the treatment of breast cancer and its related research. Berberine, also known as berberine, is a common isoquinoline, extracted from Chinese herbs such as yellow lotus and cortex Phellodendron. Berberine can inhibit tumor cell apoptosis, inhibit tumor cell proliferation, inhibit tumor cell metastasis and enhance the sensitivity of tumor cells to chemotherapeutic drugs. The relationship between berberine and breast cancer is a hot spot of research, and the study in vivo has not yet been studied Therefore, we hope to establish the animal model of breast cancer in nude mice by inoculating human breast cancer cell MCF-7 in nude mice and studying the effect and influence of berberine hydrochloride on MCF-7 breast cancer mice. Objective to establish the animal model of breast cancer by subcutaneous the human breast cancer cell line MCF-7 to the back of nude mice. Type, study the effect and influence of berberine hydrochloride on MCF-7 breast cancer mice. Method 1, inoculating cells in the right back of the mouse, establishing a nude mouse model of MCF-7 transplanted tumor of human breast cancer, and calculating the antitumor effect (TGI) of the drug (TGI). Two, HE staining method was used to detect the staining of the transplanted tumor tissue in the test groups. Three, TUN EL staining was used to detect the cell apoptosis in the transplanted tumor tissues of the experimental groups. Four, the cell cycle of the transplanted tumor tissues of the experimental groups was detected by flow cytometry. Five, the immunohistochemical SP method was used, and the expression of MMP-2, MMP-9, p53 and EGFR protein in the transplanted tumor tissues of the experimental groups was detected by Western blot. The results were 1, The growth of transplanted tumor in nude mice: (1) the weight of the rats in each group decreased at twenty-first days, with statistical difference (P0.05). (2) the volume difference between the five groups of nude mice was statistically significant (P0.05).2, the tumor inhibition rate of each group was B1, B2, B3, and the TGI values of group C were 5.55%, 4.91%, 58.88%, 67.72%, and the differences were significantly poor. Histopathological changes of xenograft tumor in nude mice: (1) naked eye: (1) naked eye: the transplanted tumor was round, round or lobulated. (2) light microscopy: tumor cells slightly increased, treatment group ISO cells decreased, tumor tissue structure destroyed.4, TUNEL staining results showed that the apoptosis index of each group was statistically different (P0.01).5, flow cytometry results The results showed: (1) the cell cycle distribution in the S period showed that there were significant differences between each group (P0.01). (2) the cell cycle distribution in Go/G1 period showed significant difference (P0.01).6, immunohistochemistry, and Western blot results showed that the expression of MMP-2, MMP-9, P53, EGFR protein in the control group Significantly higher than other experimental groups, the difference between the groups was statistically significant (P0.05). Conclusion 1. successfully established the nude mouse breast cancer MCF-7 cell subcutaneous transplantation tumor disease model.2. berberine can inhibit the growth of MCF-7 breast cancer in nude mice, and the inhibitory effect is concentration dependent.
【學(xué)位授予單位】：南方醫(yī)科大學(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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