本文選題：STK33 + Fadu細胞　； 參考：《山東大學》2016年博士論文

【摘要】：第一部分STK33促進下咽癌增殖與鈣離子相關(guān)性研究背景：下咽鱗狀細胞癌(hypopharyngeal squamous cell carcinoma, HSCC)是人類最常見的惡性腫瘤之一,多年來,雖然治療手段不斷發(fā)展,但患者的生存率未有顯著提高。普遍認為大多數(shù)腫瘤是由于包括癌基因的激活以及抑癌基因的失活的多因素作用的結(jié)果。盡管HSCC的發(fā)生和發(fā)展包含許多基因與外源因素,但是參與這種腫瘤形成的分子機制知之甚少。蛋白激酶是研究比較透徹且具多樣化特性的蛋白超級家族。絲氨酸/蘇氨酸激酶(serine/threonine kinase, STK)作為這一超級家族的成員,其功能是使蛋白質(zhì)上的絲氨酸和蘇氨酸殘基發(fā)生磷酸化,在調(diào)節(jié)諸如DNA復制、信號轉(zhuǎn)導通路、細胞增殖、細胞分化、細胞死亡及腫瘤發(fā)生和發(fā)展等重要細胞進程中發(fā)揮關(guān)鍵性的作用。絲氨酸/蘇氨酸激酶33 (STK33)調(diào)控與Ras基因存在交互依賴關(guān)系的腫瘤細胞的信號轉(zhuǎn)導,從而在腫瘤增殖過程中發(fā)揮特殊作用。STK33屬鈣離子/鈣調(diào)素依賴蛋白(calcium/calmodulin dependent kinase, CAMK)家族成員,目前數(shù)據(jù)表明,STK33通過特異性磷酸化波形蛋白從而參與細胞骨架解聚的動態(tài)過程,以及影響細胞的結(jié)構(gòu)和功能。最近,有力的證據(jù)證明STK33參與腫瘤的形成。然而,STK33在HSCC中的精確功能和機制尚未清楚,仍需進一步研究。本文旨在在我們前期研究的基礎上,進一步通過體內(nèi)實驗和Microarray分析來探索STK33的功能,重點探索STK33的改變與鈣離子的可能關(guān)系。方法：通過含有針對STK33的shRNA的慢病毒載體,感染細胞,并使用PCR法檢測慢病毒感染后Fadu細胞中STK33 mRNA表達的變化。進行Microarray分析,尋找STK33基因敲除后的表達譜變化。注射Fadu細胞,Mock空載體細胞,以及STK33基因敲除細胞于5周雄性裸鼠右側(cè)腋下進行皮下注射,定期測量腫瘤大小,并計算腫瘤體積,待對照組的腫瘤直徑達到1.5厘米時,收獲腫瘤和肺組織。在進行蘇木素伊紅染色后,使用顯微鏡觀察腫瘤和肺的形態(tài)學改變,以了解Fadu細胞在體內(nèi)成瘤和侵襲轉(zhuǎn)移的能力。進行免疫組化分析STK33蛋白的表達。使用MTT和吖啶橙染色檢測Ionomycin對Fadu細胞存活力及形態(tài)學改變的影響。通過使用Fluo-3/AM染色,借助共聚焦顯微鏡對細胞內(nèi)鈣離子的濃度進行檢測。使用實時熒光定量PCR及western blot檢測相關(guān)基因的mRNA及蛋白的表達情況。結(jié)果：STK33-RNAi穩(wěn)定表達的Fadu細胞,感染空載體的Fadu細胞和對照Fadu細胞皮下注射到雄性裸鼠右側(cè)腋下后第14天對照Fadu細胞成瘤,共生長39天�？蛰d體對照組和對照Fadu細胞組表現(xiàn)出相似的生長率,在第39天時,體積達到約570mm3。然而,穩(wěn)定轉(zhuǎn)染的STK33-RNAi表達的Fadu細胞在裸鼠體內(nèi)生長緩慢,在39天僅形成較小的腫瘤,體積約為90 mm3。在STK33表達和不表達的細胞中腫瘤的體積有顯著差異。這表明STK33促進HSCC在體內(nèi)的形成。免疫組化結(jié)果顯示STK33在STK33-RNAi細胞中的表達比載體對照組的細胞弱。注射對照組細胞的裸鼠的肺顯示存在轉(zhuǎn)移；相反,在注射STK33-RNAi細胞的裸鼠中未見轉(zhuǎn)移。通過Microarray分析,在STK33-RNAi細胞中,我們發(fā)現(xiàn)了140個有顯著差異的標記基因。這些基因顯著(p0.05)上調(diào)(n=86)或者下調(diào)(n=54)。通過通路分析,我們發(fā)現(xiàn)STK33影響很多基因的表達,調(diào)節(jié)很多通路。從中我們發(fā)現(xiàn)了Calpainl(CAPN1),并用qRT-PCR確認CAPN1的mRNA表達水平。在STK33-RNAi Fadu細胞中CAPN1的表達顯著下降(pO. 05)。Ionomycin可以迅速升高細胞內(nèi)鈣離子的濃度。在1.5 μM的Ionomycin作用6小時后進行吖啶橙染色發(fā)現(xiàn)未處理的細胞呈現(xiàn)多邊形,然而,典型的凋亡特點出現(xiàn)在Ionomycin處理的細胞中,包括細胞形態(tài)不規(guī)則,細胞皺縮,染色質(zhì)凝集,染色小體出現(xiàn),表明Ionomycin可以誘導Fadu細胞凋亡。細胞存活率在Fadu細胞中顯示出明顯的隨Ionomycin作用時間延長而降低的趨勢。表明Ionomycin抑制細胞存活率呈現(xiàn)時間依賴性。在STK33-RNAi作用后細胞存活率顯著下降。此外,在STK33-RNAi與Ionomycin同時作用后,細胞存活率下降程度低于僅Ionomycin作用(p0.05)。與未處理的Fadu細胞相比,STK33的蛋白表達在1.5 μM Ionomycin作用1,2,4,6小時后升高。統(tǒng)計分析表明STK33的蛋白表達在作用1,2,4,6小時后比對照組顯著升高(p0.05)。這表明,Ionomycin可以增高STK33蛋白的表達。Fadu細胞中的CAPN1在1.5 μM Ionomycin作用1,2,4,6及24小時后CAPN1顯著升高(p0.05)。但在STK33-RNAi組中,作用前后沒有顯著性差異。結(jié)論：shRNA介導的STK33基因的敲除抑制Fadu細胞在體內(nèi)的成瘤能力,從而證明STK33本身對腫瘤生長的促進作用。表明STK33在腫瘤形成中發(fā)揮重要作用。此外,通過免疫組化發(fā)現(xiàn)STK33在STK33-RNAi組所成腫瘤中的表達明顯下降。這表明STK33-RNAi仍然發(fā)揮它對STK33的敲除作用,藉以表明Fadu細胞在以STK33-RNAi抗腫瘤影響的基礎上的增值能力的降低�？傊�,體內(nèi)實驗進一步證實了我們前期的從體外及臨床切除樣本中得到的STK33是一個潛在癌基因的研究結(jié)果。STK33基因通過多種信號通路在Fadu細胞中發(fā)揮作用。這個過程中包含大量決定腫瘤進展中的重要功能的基因。CAPN1,在STK33-RNAi的干擾下顯著下調(diào),正如本研究中進一步PCR所證明的。本研究表明CAPN1的活性受STK33-RNAi的影響,提示CAPN1涉及STK33在Fadu細胞中誘導腫瘤形成的作用。這個發(fā)現(xiàn)可能是一個很有吸引力的線索,在Fadu細胞中,STK33可能與鈣離子有關(guān)。因為STK33屬于CAMK家族。這促使我們關(guān)注STK33活性與Ionomycin作用后Fadu細胞內(nèi)鈣離子改變的關(guān)系。Ionomycin可以在體外抑制Fadu細胞的生長。這表明Ionomycin通過提高細胞內(nèi)鈣離子濃度來表現(xiàn)出它對Fadu細胞的毒性作用。有意思的是,STK33-RNAi可以在一定程度上抵消Ionomycin引起的細胞損傷。表明STK33敲除可能保護細胞不受Ionomycin觸發(fā)的高細胞內(nèi)鈣離子濃度而引起的細胞損傷。這為細胞內(nèi)游離鈣離子可能通過STK33活性來影響CAPN1表達,從而影響一些與STK33在腫瘤發(fā)生中重要作用相關(guān)的重要的信號轉(zhuǎn)導通路,提供了證據(jù)�？傊�,本研究進一步證明了STK33是一個潛在的癌基因,它通過調(diào)節(jié)眾多基因在HSCC腫瘤發(fā)生中發(fā)揮重要作用。另外,在Fadu細胞內(nèi)的STK33和鈣離子存在相互的影響。第二部分NGFR在ESM1介導的口腔鱗狀細胞癌腫瘤發(fā)生中的作用研究背景：口腔鱗狀細胞癌(oral squamous cell carcinoma, OSCC)是人類最常見的惡性腫瘤之一。近年來,其生存率并沒有隨著治療手段的迅速發(fā)展而明顯改善。這種情況主要因為遠處轉(zhuǎn)移以及治療耐受的復發(fā)。對于為什么某些細胞對化療和放療更加耐藥的生物學解釋來自支持在惡性腫瘤中有一組細胞賦予“干細胞”樣屬性的觀點。我們實驗室最近發(fā)現(xiàn)了一個在OSCC中的腫瘤起始細胞的新的標志,我們認為它可以解決我們剛剛提到的困境。這個標志就是低親和力的神經(jīng)生長因子受體(nerve growth factor receptor, NGFR), NGFR是頭頸鱗狀細胞癌進展、轉(zhuǎn)移和生存中的腫瘤起始細胞的一個功能和可命中目標的標志物。它的激活導致NF-κB(核因子-K B),Jun激酶以及其他信號通路的活化,從而發(fā)揮重要的生物學功能。NGFR在OSCC中的確切功能和機制已經(jīng)被研究了,但是還有不清楚的地方。本研究在我們前期研究的基礎上,設計通過小鼠OSCC細胞的Microarray分析和體內(nèi)外實驗來進一步探索NGFR的功能。方法：使用實時熒光定量PCR、流式細胞術(shù)及ELISA實驗檢測相關(guān)基因的mRNA和蛋白的表達情況。通過慢病毒感染細胞,穩(wěn)定過表達MOC2細胞中的NGFR(MOC2T),進行Microarray分析,尋找NGFR基因過表達后的表達譜變化。通過慢病毒感染細胞,穩(wěn)定過表達MOC2細胞中的ESM1,敲除ESM1在MOC2和MOC2T細胞中的表達。使用MTT和Transwell侵襲轉(zhuǎn)移實驗分析ESM1口NGFR對細胞增殖和侵襲轉(zhuǎn)移能力的影響。注射MOC2, MOC2-7, MOC2-10, MOC2-ESM1-SH, MOC2T和MOC2T-ESM1-SH細胞于6-11周B10; B6-Rag2-/-II2rg-/-小鼠右側(cè)后腿背側(cè)進行皮下注射,定期測量腫瘤大小,并計算腫瘤體積,收獲腫瘤和肺組織。在進行蘇木素伊紅染色后,使用顯微鏡觀察腫瘤和肺的形態(tài)學改變。檢測ESM1是否參與血管形成,進行免疫熒光分析血管內(nèi)皮生長因子(vascular endothelial growth factor, VEGF)的表達。結(jié)果：通過qRT-PCR檢測發(fā)現(xiàn),NGFR在小鼠OSCC細胞系(MOC2,MOC2-7和MOC2-10)中表達。通過慢病毒感染,形成NGFR穩(wěn)定過表達的MOC2細胞株,通過Microarray分析尋找NGFR過表達后的基因表達譜改變。通過對Microarray結(jié)果的分析,我們發(fā)現(xiàn)了內(nèi)皮細胞特異性分子-1(endothelial cell specific molecule 1, ESM1)。 ESM1是一種新型的內(nèi)皮衍生的水溶性硫酸皮膚蛋白多糖,具有廣泛結(jié)合與細胞信號和粘附相關(guān)的生物活性分子的能力,從而調(diào)節(jié)健康和疾病中的不同類型細胞的增殖,分化,轉(zhuǎn)移和粘附。NGFR依賴的ESM1的mRNA水平的表達在NGFR過表達和NGF處理的細胞中得到驗證。ESM1的表達水平與小鼠OSCC細胞系的增殖和侵襲轉(zhuǎn)移能力成正相關(guān)。ESM1過表達誘導MOC2細胞活力,遷移和侵襲能力。相反,ESM1的敲除抑制MOC2細胞的增殖,遷移和侵襲能力。免疫缺陷小鼠皮下移植瘤表明ESM1的敲除減小腫瘤大小和肺轉(zhuǎn)移的克隆數(shù)目。降低NGFR過表達的MOC2細胞(MOC2T)的ESM1的表達也可以在體內(nèi)及體外降低MOC2T腫瘤增殖以及侵襲和轉(zhuǎn)移能力�？傊�,這是第一次報告ESM1是NGFR的一個靶點,從而為NGFR和ESM1之間提供了一個新的互連。我們發(fā)現(xiàn),ESM1敲除在體內(nèi)和體外減少MOC2細胞的增殖和轉(zhuǎn)移,因而提示NGFR通過它所調(diào)節(jié)的基因來誘導增殖和轉(zhuǎn)移。此外,ESM1單獨或與NGFR結(jié)合可能作為OSCC的新的預后生物標志物,也可能描繪了針對OSCC的創(chuàng)新的治療方法。
[Abstract]:The first part STK33 promotes the relationship between the proliferation of hypopharyngeal carcinoma and the calcium ion: hypopharyngeal squamous cell carcinoma (HSCC) is one of the most common malignant tumors in human. For many years, the survival rate of the patients has not been significantly improved. It includes the activation of oncogenes and the multifactor effects of inactivation of the tumor suppressor genes. Although the occurrence and development of HSCC include many genes and exogenous factors, little is known about the molecular mechanism involved in the formation of this tumor. Protein kinase is a more thorough and diversified protein superfamily. Serine / threonine excitation Serine/threonine kinase (STK), as a member of this superfamily, has the function of phosphorylating the serine and threonine residues on the protein and plays a key role in regulating important cell processes, such as DNA replication, signal transduction, cell proliferation, cell differentiation, cell death and tumorigenesis and development. Tyrosine / threonine kinase 33 (STK33) regulates the signal transduction of tumor cells interacting with the Ras gene, which plays a special role in the proliferation of.STK33 family members of the calcium/calmodulin dependent kinase (CAMK) family of calcium ion / calmodulin dependent protein (CAMK). The current data show that STK33 through specific phosphorylation Vimentin is involved in the dynamic process of cytoskeleton depolymerization, as well as the structure and function of cells. Recently, strong evidence has shown that STK33 is involved in the formation of tumors. However, the precise function and mechanism of STK33 in HSCC are still not clear, and further study is needed. Experiments and Microarray analysis to explore the function of STK33, focus on exploring the possible relationship between the changes of STK33 and calcium ions. Methods: by using the lentivirus vector containing shRNA for STK33, infected cells, and using PCR to detect the alteration of STK33 mRNA expression in Fadu cells after the infection of lentivirus infection. Microarray analysis, to find STK33 gene knockout. Fadu cells, Mock no-load cells, and STK33 gene knockout cells were injected subcutaneously at the right arm of the male nude mice in 5 weeks. The tumor size was measured regularly and the tumor volume was calculated. The tumor and lung tissue were harvested when the diameter of the control group reached 1.5 cm. The morphological changes of tumor and lung were observed by microscopes in order to understand the ability of Fadu cells to be tumorigenic and invasive in the body. Immunohistochemical analysis of the expression of STK33 protein. The effects of Ionomycin on the viability and morphological changes of Fadu cells were detected by MTT and acridine orange staining. By using Fluo-3/AM staining, confocal microscopy was used. Detection of intracellular calcium concentration. The expression of mRNA and protein of related genes was detected by real-time fluorescent quantitative PCR and Western blot. Results: STK33-RNAi stable Fadu cells, Fadu cells infected with empty carrier and control Fadu cells were injected subcutaneously into the right lateral axillary of male nude mice for fourteenth days to compare with Fadu cells to form a tumor. The growth rate was similar to that of the control group and the control Fadu cell group for 39 days. At thirty-ninth days, the volume reached about 570mm3., but the Fadu cells expressed by the stable transfected STK33-RNAi were slowly growing in the nude mice, and only a smaller tumor was formed on the 39 day, and the volume was about 90 mm3. in the STK33 and unexpressed cells. There were significant differences. This indicates that STK33 promotes the formation of HSCC in the body. The immunohistochemical results show that the expression of STK33 in STK33-RNAi cells is weaker than that in the carrier control group. The lung display of the nude mice injected with the control group is metastatic; on the contrary, there is no metastasis in the nude mice injected with STK33-RNAi cells. Microarray analysis, in STK33- In RNAi cells, we found 140 marked differentially marked genes. These genes were significantly (P0.05) up-regulated (n=86) or down down (n=54). Through pathway analysis, we found that STK33 affects many genes and regulates many pathways. We found Calpainl (CAPN1), and confirmed CAPN1's mRNA expression with qRT-PCR. In STK33-RNAi. The expression of CAPN1 in Fadu cells decreased significantly (pO. 05).Ionomycin could rapidly increase the concentration of intracellular calcium. After 6 hours of Ionomycin action of 1.5 mu M, acridine orange staining showed that the untreated cells presented polygons. However, typical apoptotic characteristics appeared in the cells treated with Ionomycin, including irregular cell morphology. Cell crinkle, chromatin agglutination, and dyed corpuscle appeared, indicating that Ionomycin could induce apoptosis of Fadu cells. The survival rate of cell in Fadu cells showed a tendency to decrease with the prolongation of the time of Ionomycin action. It showed that the survival rate of Ionomycin inhibited cells was time dependent. The survival rate of cells decreased significantly after the action of STK33-RNAi. In addition, after the simultaneous action of STK33-RNAi and Ionomycin, the decrease of cell survival rate was lower than that of Ionomycin only (P0.05). Compared with untreated Fadu cells, the protein expression of STK33 increased after 1.5 u M Ionomycin in 1,2,4,6 hours. The statistical analysis showed that the protein expression of STK33 was significantly higher than that of the control group after the action 1,2,4,6 hours (P0.05). This indicates that Ionomycin can increase the expression of CAPN1 in the expression of STK33 protein in.Fadu cells in 1,2,4,6 and 24 hours after 1,2,4,6 and CAPN1 significantly increased (P0.05). But in the STK33-RNAi group, there is no significant difference before and after action. Conclusion: shRNA mediated STK33 gene knockout inhibits the tumorigenicity of.Fadu cells in the body. STK33 itself promotes the growth of tumor. It shows that STK33 plays an important role in the formation of tumor. In addition, the expression of STK33 in the tumor of STK33-RNAi group is obviously decreased by immunohistochemistry. This indicates that STK33-RNAi still plays a knockout effect on STK33, which indicates that Fadu cells are on the basis of the anti tumor effect of STK33-RNAi. In conclusion, in vivo experiments further confirmed that our earlier STK33 from in vitro and clinically excised samples is a potential oncogene study that the.STK33 gene plays a role in Fadu cells through a variety of signaling pathways. This process includes a large number of important functions that determine the progression of cancer. Gene.CAPN1, down significantly under the interference of STK33-RNAi, as demonstrated by further PCR in this study. This study showed that the activity of CAPN1 was affected by STK33-RNAi, suggesting that CAPN1 involves the role of STK33 in inducing tumor formation in Fadu cells. This discovery may be a very attractive clue, in Fadu cells, STK33 may be associated with calcium. Ions are related, because STK33 belongs to the CAMK family. This has prompted us to focus on the relationship between STK33 activity and the changes in calcium ions in Fadu cells after the action of Ionomycin..Ionomycin can inhibit the growth of Fadu cells in vitro. This indicates that Ionomycin shows its toxic effect on Fadu cells by increasing intracellular calcium concentration. It is interesting, STK. 33-RNAi can counteract the cell damage caused by Ionomycin to a certain extent. It shows that STK33 knockout may protect cells from cell damage caused by high intracellular calcium ion concentration triggered by Ionomycin, which may affect the expression of CAPN1 through the activity of STK33 in the cell, which may affect some of the STK33 in the carcinogenesis of the tumor. The important signal transduction pathway related to the important role, provided evidence. In conclusion, this study further demonstrated that STK33 is a potential oncogene, which plays an important role in the development of HSCC tumors by regulating many genes. In addition, the STK33 and calcium ions in the Fadu cells are interacting with each other. The second part of NGFR is mediated by ESM1. The role of oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in human oral squamous cell carcinoma. In recent years, the survival rate has not improved obviously with the rapid development of treatment. This situation is mainly due to the distant metastasis and the recovery of the treatment tolerance. The biological explanation for why some cells are more resistant to chemotherapy and radiation comes from the view that a group of cells give a "stem cell" like attribute in the malignant tumor. Our laboratory recently discovered a new marker of the tumor starting cells in OSCC, and we think it can solve the difficulties we have just mentioned. This symbol is a low affinity nerve growth factor receptor (NGFR), and NGFR is a function and target marker for the progression, metastasis and survival of cancer starting cells in the head and neck squamous cell carcinoma. Its activation leads to the survival of NF- kappa B (nuclear factor -K B), Jun kinase, and other signaling pathways. The exact function and mechanism of the important biological function,.NGFR, has been studied in OSCC, but there is no clear place. On the basis of our previous study, this study was designed to further explore the function of NGFR through the Microarray analysis of mouse OSCC cells and in vivo and in vivo. Methods: using real time fluorescence determination. PCR, flow cytometry and ELISA test to detect the expression of mRNA and protein related genes. Through the lentivirus infected cells, stable overexpression of NGFR (MOC2T) in MOC2 cells, Microarray analysis was carried out to find the expression profiles of NGFR gene overexpression. Through the lentivirus infected cells, the ESM1 of the MOC2 cells was stably expressed and the ES was knocked out of ES. M1 expression in MOC2 and MOC2T cells. Use MTT and Transwell invasion and metastasis test to analyze the effect of ESM1 mouth NGFR on cell proliferation and invasion and metastasis. Injection MOC2, MOC2-7, MOC2-10, MOC2-ESM1-SH, MOC2T, and cells at 6-11 weeks; subcutaneous injection on the back of the right hind leg of the right mouse. The size of the tumor and the volume of the tumor were calculated and the tumor and lung tissue were harvested. After hematoxylin staining, the morphological changes of the tumor and lung were observed by microscope. Whether ESM1 was involved in angiogenesis and the expression of vascular endothelial growth factor (vascular endothelial growth factor, VEGF) was analyzed by immunofluorescence. Results: through qRT-PC R detection showed that NGFR was expressed in the mouse OSCC cell line (MOC2, MOC2-7 and MOC2-10). Through the infection of the lentivirus, the MOC2 cell line that was stable and overexpressed in NGFR was formed, and the gene expression profiles after the NGFR overexpressed were found by Microarray analysis. Ell specific molecule 1, ESM1). ESM1 is a new type of endothelium derived water-soluble sulfonated skin proteoglycan that has the ability to combine with cell signaling and adhesion related bioactive molecules to regulate the proliferation, differentiation, transfer and adhesion of.NGFR dependent ESM1 mRNA levels in different types of cells in health and disease. Expression in NGFR overexpressed and NGF treated cells showed that the expression level of.ESM1 was positively related to the proliferation and invasion and metastasis of OSCC cell lines in mice..ESM1 overexpression induced MOC2 cell viability, migration and invasion ability. On the contrary, ESM1 knockout inhibited the proliferation, migration and invasion of MOC2 cells. Subcutaneous transplantation of immune deficient mice. The tumor indicates that the ESM1 knockout reduces the number of tumor size and the number of clones of the lung metastasis. The ESM1 expression of the MOC2 cells (MOC2T) that reduces the overexpression of NGFR can also reduce the proliferation and invasion and metastasis of MOC2T in vivo and in vitro. In a word, this is the first report that ESM1 is a target for NGFR, thus providing one between NGFR and ESM1. New interconnection. We have found that ESM1 knocks down the proliferation and metastasis of MOC2 cells in vivo and in vitro, thus suggesting that NGFR can induce proliferation and metastasis through its regulated genes. In addition, the combination of ESM1 alone or with NGFR may serve as a new prognostic biomarker for OSCC, and may also describe an innovative treatment for OSCC.

【學位授予單位】：山東大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R739.91

【相似文獻】

相關(guān)期刊論文 前10條

1 丁志山，沃興德;細胞調(diào)亡與動脈粥樣硬化[J];中國動脈硬化雜志;1998年01期

2 李妍;紀朋艷;張巍;彭順利;呂士杰;;柴胡皂苷d對SH-SY5Y細胞ERK蛋白表達及凋亡的影響[J];中國醫(yī)科大學學報;2013年12期

3 嚴銀芳,陳曉,楊小清,閆遠芳;流行性腮腺炎病毒減毒株S_(79)在幾株腫瘤細胞和正常細胞中增殖的比較研究[J];腫瘤;2003年06期

4 劉功讓;管培中;宋淑亮;逯素梅;馮玉新;辛華;;絞股藍多糖對四氯化碳損傷HepG2細胞的保護作用[J];山東醫(yī)藥;2007年31期

5 肖東杰,汪運山;B細胞被動凋亡的研究進展[J];國外醫(yī)學(臨床生物化學與檢驗學分冊);1998年05期

6 張運濤,劉凡,姜茹,谷仲平,汪涌,張順,劉榮福,李玉梅;外源性p27與GRC-1細胞端粒酶活性及細胞凋亡關(guān)系的實驗研究[J];中國現(xiàn)代醫(yī)學雜志;2002年09期

7 石和元;王平;胡永年;邱幸凡;田代志;;溫膽湯改良方對Aβ_(25-35)誘導AD細胞模型bcl-2、bax蛋白表達的影響[J];世界科學技術(shù);2005年06期

8 孟威宏;王強;王虹蛟;顏煒群;;牛胰蛋白酶抑制劑研究進展[J];國外醫(yī)學(老年醫(yī)學分冊);2008年04期

9 鐘民濤;王曉麗;李星云;劉磊;劉穎麗;張偉;黃敏;;香菇C91-3菌絲發(fā)酵蛋白對H22腫瘤細胞體內(nèi)外抗腫瘤機制的初探[J];中國微生態(tài)學雜志;2011年09期

10 張晨,黃世林,馬東初,孫英慧,馬小鋒;硫化砷誘導NB_4細胞調(diào)亡[J];白血病;2000年06期

相關(guān)會議論文 前10條

1 鄒萍;;血液系統(tǒng)惡性腫瘤細胞來源膜微粒的特征及生物學作用研究[A];第13屆全國實驗血液學會議論文摘要[C];2011年

2 蔣爭凡;卞婕;翟中和;;非細胞體系誘導小鼠肝細胞核凋亡的超微觀察[A];第十次全國電子顯微學會議論文集（Ⅰ）[C];1998年

3 陳衛(wèi)銀;祝彼得;劉福友;馮雪梅;;參芎滴丸對急性腦梗死模型大鼠神經(jīng)細胞調(diào)亡的影響[A];中華醫(yī)學會第十三次全國神經(jīng)病學學術(shù)會議論文匯編[C];2010年

4 謝晶日;李威;梁國英;楊豐源;;胃靈顆粒對胃癌前病變細胞調(diào)亡基因影響的實驗研究[A];中華中醫(yī)藥學會脾胃病分會第十八次學術(shù)交流會論文匯編[C];2006年

5 綦淑芬;萬瑞香;姚如勇;;扇貝多肽對Hela細胞在紫外線損傷下的保護作用[A];第五屆全國自由基生物學與自由基醫(yī)學學術(shù)討論會論文摘要匯編[C];2000年

6 吳李君;裴蓓;王順昌;王軍;湯明禮;;砷和鎘暴露誘導秀麗小桿線蟲生殖腺細胞調(diào)亡及其信號通路研究[A];中國毒理學會第二屆全國中青年學者科技論壇會議論文集[C];2007年

7 余珂;王敬賢;周炳升;;多溴聯(lián)苯醚誘導人神經(jīng)SK-N-SH細胞調(diào)亡的機理[A];湖北省暨武漢市生物化學與分子生物學學會第八屆第十七次學術(shù)年會論文匯編[C];2007年

8 冉新澤;鄭懷恩;王艾平;王鋒超;韓京;;他汀對內(nèi)皮細胞輻射損傷組織因子與細胞調(diào)亡的影響[A];中國毒理學會放射毒理專業(yè)委員會第七次、中國毒理學會免疫毒理專業(yè)委員會第五次、中國環(huán)境誘變劑學會致突專業(yè)委員會第二次、中國環(huán)境誘變劑學會致畸專業(yè)委員會第二次、中國環(huán)境誘變劑學會致癌專業(yè)委員會第二次全國學術(shù)會議論文匯編[C];2008年

9 崔承彬;閆少羽;蔡兵;趙慶春;姚新生;曲戈霞;;黑果黃皮Clausena dunniana Levl中咔唑生物堿類新細胞周期抑制劑及細胞調(diào)亡誘導劑的核磁共振研究[A];第十一屆全國波譜學學術(shù)會議論文摘要集[C];2000年

10 吳耀輝;鄒萍;;Sunrivin基因沉默對K562細胞調(diào)亡影響的研究[A];第11次中國實驗血液學會議論文匯編[C];2007年

相關(guān)重要報紙文章 前1條

1 張?zhí)锟?細胞調(diào)亡的意義[N];中國人口報;2002年

相關(guān)博士學位論文 前10條

1 羅曉明;載藥聚合物超細纖維作為腫瘤局部制劑的研究[D];西南交通大學;2014年

2 王石;黃芪甲苷促進血管新生的分子機制研究[D];南京中醫(yī)藥大學;2013年

3 宋楊;抗CD25單抗對腎移植患者調(diào)節(jié)性T細胞生存和功能改變影響的研究[D];復旦大學;2014年

4 羅忠光;CRL E3泛素連接酶靶向新藥MLN4924在體內(nèi)外殺傷肝癌細胞的作用及機制研究[D];復旦大學;2014年

5 肖林林;巨噬細胞對血管細胞的輻射旁效應及其分子機制研究[D];復旦大學;2014年

6 張峰;戊型肝炎病毒基因4型在PLC/PRF/5細胞中的培養(yǎng)及其特征研究[D];北京協(xié)和醫(yī)學院;2014年

7 陳鳳華;Tat-SmacN7融合肽對腫瘤細胞輻射增敏作用的研究[D];北京協(xié)和醫(yī)學院;2013年

8 虞志新;Th17/Treg失衡及其與中性粒細胞相互影響在ARDS發(fā)病中的作用和機制研究[D];江蘇大學;2015年

9 黃凌燕;STK33基因在下咽鱗狀細胞癌發(fā)生發(fā)展中的作用機制研究[D];山東大學;2015年

10 袁媛;let-7c介導c-Myc基因調(diào)控逆轉(zhuǎn)肝癌細胞多藥耐藥的機制研究[D];蘭州大學;2015年

相關(guān)碩士學位論文 前10條

1 王帥帥;Marc-145細胞中豬繁殖與呼吸綜合癥病毒粒子與胞外體的分離與鑒定[D];山西農(nóng)業(yè)大學;2015年

2 杜文娟;NK-lysin通過Wnt/β-catenin信號通路抑制肝癌細胞侵襲與轉(zhuǎn)移的研究[D];山西農(nóng)業(yè)大學;2015年

3 張曉嬌;天然抗氧化劑對乳腺癌MCF-7/ADM細胞的耐藥逆轉(zhuǎn)作用及機制研究[D];河北聯(lián)合大學;2014年

4 呂超紹;重組人干擾素γ(rhIFN-γ)對白血病K562細胞免疫逃逸的影響[D];昆明理工大學;2015年

5 汪建陽;Ang-(1-7)通過G蛋白偶聯(lián)受體Mas對人肝癌HepG2細胞的影響研究[D];廣西醫(yī)科大學;2015年

6 任志濤;小檗堿對TGF-β1誘導A549細胞上皮間質(zhì)轉(zhuǎn)化和MRC-5細胞轉(zhuǎn)分化及細胞信號通路相關(guān)蛋白的影響[D];北京協(xié)和醫(yī)學院;2015年

7 楊曉姍;重組人p66Shc腺病毒和賴氨藤黃酸鹽對腫瘤細胞的抑制作用及機制[D];北京協(xié)和醫(yī)學院;2015年

8 萬愛英;大分割照射生物效應實測數(shù)據(jù)與LQ公式計算數(shù)據(jù)的比較研究[D];北京協(xié)和醫(yī)學院;2015年

9 邢曉萌;白藜蘆醇對肺癌A549細胞的放射增敏作用及其機制研究[D];北京協(xié)和醫(yī)學院;2015年

10 曹曰針;胞外泛素對Treg細胞免疫抑制活性的影響[D];復旦大學;2014年

，

本文編號：1819377