本文選題：PARP抑制劑 + 乳腺癌��； 參考：《新鄉(xiāng)醫(yī)學院》2015年碩士論文

【摘要】：背景腫瘤干細胞學說認為,惡性腫瘤中的干細胞亞群具有自我更新和多項分化的能力,是惡性腫瘤復發(fā)、轉(zhuǎn)移的根本原因。聚腺苷酸二磷酸核糖轉(zhuǎn)移酶(poly ADP-ribose polymerase,PARP)在細胞中的主要功能為對損傷、斷裂的DNA鏈進行識別和修復,臨床上對乳腺癌進行的放療、化療的主要作用機制即為損傷和破壞腫瘤細胞的DNA,從而造成腫瘤細胞的死亡,PARP被認為是導致惡性腫瘤對放療、化療產(chǎn)生抗性的重要原因,所以它也成為了治療乳腺癌的一個新靶點。鹽霉素是一種已經(jīng)經(jīng)實驗證實的對乳腺癌干細胞具有殺傷作用的藥物。依維莫司是一種哺乳動物雷帕霉素靶蛋白(mTOR)抑制劑,臨床主要用于器官移植后的免疫抑制及抗腫瘤應(yīng)用。舒尼替尼是一種多靶點酪氨酸激酶抑制劑,臨床上主要用于晚期腎細胞癌(renal cell carcinoma ,RCC)和胃腸道間質(zhì)瘤(gastrointestinal stromal tumor, GIST)的治療。目的分別對經(jīng)過PARP抑制劑、鹽霉素、依維莫司、舒尼替尼處理后的乳腺癌細胞和未經(jīng)過藥物處理的空白組細胞中的干細胞亞群進行標記,對比兩組細胞中干細胞群所占比例,探究各種藥物對腺癌干細胞有無抑制作用。方法取三陰性乳腺癌細胞株BT-20細胞,用不同濃度的5種藥物分別對BT-20細胞進行處理,計算出各種藥物的半數(shù)抑制濃度,從中挑選出各自藥物的合適濃度(對BT-20細胞的抑制率為10%左右),用5種藥物對BT-20細胞再次進行處理,ALDEFLUOR試劑標記出加藥細胞組和未加藥細胞的ALDH1+細胞,利用流式細胞儀檢測并對比兩組細胞間ALDH1陽性細胞比例,檢驗藥物對干細胞亞群的抑制作用。結(jié)果Veliparib.Olaparib.Iniparib.鹽霉素、依維莫司、舒尼替尼的ICso分別為32.23、38.65、35.12、7.21、5.73、7.85μmol/L。未加藥組細胞中的ALDH1+細胞比例為(19.34±1.15)%,實驗組細胞中的ALDHl+細胞比例為(鹽霉素,1μmol/L)(10.87±2.24)%；(鹽霉素,2μmol/L)(6.33±1.52)%；(Olaparib,10μmol/L)(8.45±0.56)%； (Veliparib,10μmol/L)(13.27±2.14)%；(Iniparib,10μmol/L)(6.83±2.67)%；(依維莫司,1μmol/L)(9.82±1.74)%；(舒尼替尼,1μmol/L)(7.87±2.52)%.實驗組細胞的ALDH1+細胞比例顯著降低,(P0.05)。結(jié)論經(jīng)PARP抑制劑(Veliparib、Olaparib、Iniparib)、鹽霉素、依維莫司、舒尼替尼作用后的BT-20細胞中ALDH1+細胞比例明顯降低,以上藥物對乳腺癌細胞株BT-20中的干細胞亞群有直接抑制作用。Primary research of the inhibition of PARP inhibitor,Salinomycin, Everolimus and Sunitinib on breast cancer BT-20 stem cells
[Abstract]:Background: according to the theory of tumor stem cells, stem cell subsets in malignant tumors have the ability of self-renewal and multi-differentiation, which is the fundamental cause of recurrence and metastasis of malignant tumors.The main function of polyadenylate diphosphate ribonucleosyltransferase (ADP-ribose) in cells is to recognize and repair the damaged and broken DNA chains, and to treat breast cancer with radiotherapy.The main mechanism of chemotherapy is to damage and destroy the DNA of tumor cells, resulting in the death of tumor cells. PARP is considered to be an important cause of cancer resistance to radiotherapy and chemotherapy.So it has become a new target for breast cancer.Salinomycin is a proven drug that can kill breast cancer stem cells.Evimostr is a mammalian rapamycin target protein mTOR-inhibitor, which is mainly used for immunosuppressive and antitumor applications after organ transplantation.Sulnitinib is a multitarget tyrosine kinase inhibitor, which is mainly used in the treatment of advanced renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST).Objective to label the stem cell subsets in breast cancer cells treated with PARP inhibitor, salinomycin, ivimostatin and sunitinib, and to compare the proportion of stem cell groups in the two groups.To explore the inhibitory effect of various drugs on adenocarcinoma stem cells.Methods three negative breast cancer cell line BT-20 cells were treated with different concentrations of 5 drugs to calculate the half inhibitory concentration of each drug.The appropriate concentration of each drug was selected (the inhibition rate on BT-20 cells was about 10%), and ALDH1 cells were labeled with ALDEFLUOR reagent in addition cells and untreated cells with 5 kinds of drugs, and then the cells were labeled with ALDEFLUOR reagent, and the cells were labeled with ALDEFLUOR reagent, and the ALDH1 cells were labeled with ALDEFLUOR reagent.Flow cytometry was used to detect and compare the ratio of ALDH1 positive cells between the two groups, and the inhibitory effect of drugs on stem cell subsets was tested.Results Veliparib.Olaparib.Iniparib.The ICso of salinomycin, ivimostr and sulnitinib were 32.2338.65 渭 mol / L, 35.127.21 and 5.73 渭 mol / L.鏈姞鑽粍緇嗚優(yōu)涓殑ALDH1 緇嗚優(yōu)姣斾緥涓，

本文編號：1769226