BCL6B對人結(jié)直腸癌細胞SW480和LoVo增殖和遷移的影響及其機制探討
發(fā)布時間：2018-07-31 09:52
【摘要】：研究背景與目的結(jié)直腸癌(Colorectal cancer,CRC)為常見的消化道腫瘤,在全球每年約有100萬新增病例及50萬死亡病例。在我國,隨人口老齡化及致癌因素的增加,CRC發(fā)病率呈逐年上升趨勢。現(xiàn)如今,CRC難于早期診斷,其治療以手術(shù)切除為主,轉(zhuǎn)移和復發(fā)仍是導致CRC患者低生存率的主要原因。因此,闡明CRC發(fā)病的分子機制尤為重要,可為其早期診斷、治療及預后等提供新的思路。B細胞淋巴瘤6B(B cell lymphoma 6 member B,BCL6B)基因位于人17號染色體短臂1區(qū)3帶1亞帶,屬于B細胞淋巴瘤6(B cell lymphoma 6,BCL6)超家族成員,其廣泛表達于人體正常組織,然而在多種腫瘤中則發(fā)生不同位點的缺失或突變;因啟動子區(qū)DNA高甲基化導致的BCL6B表達缺失或下調(diào)普遍存在于胃癌、肝癌及CRC中,且其啟動子甲基化程度與腫瘤的惡性程度及患者不良預后呈正相關(guān);在CRC中,BCL6B的低表達與腫瘤TNM分期、淋巴轉(zhuǎn)移及放化療敏感性相關(guān),增加CRC細胞系中BCL6B的表達可激活p53信號通路發(fā)揮抗CRC的作用。這些都提示BCL6B可能是一個抑癌基因。目前,關(guān)于BCL6B在腫瘤中的作用及機制的報道尚少。本研究擬檢測和比較人正常腸上皮細胞系FHC及具有高轉(zhuǎn)移潛能的CRC細胞系SW480和Lo Vo中BCL6B的表達水平,研究BCL6B對CRC細胞增殖、遷移及侵襲能力的影響,并進一步探討其相關(guān)分子機制,為闡明BCL6B在CRC發(fā)生發(fā)展中的作用和CRC發(fā)生發(fā)展的機制積累實驗依據(jù),也為CRC的診治提供新的思路。方法1.人正常腸上皮細胞及人CRC細胞系中BCL6B內(nèi)源性表達的檢測:通過RT-PCR、q PCR和Western blot檢測人正常腸上皮細胞系FHC及CRC細胞系SW480和Lo Vo中BCL6B的表達,比較癌細胞與正常細胞之間的表達差異。2.重組質(zhì)粒pc DNA3.1-BCL6B和pc DNA3.1的擴增和驗證:將攜帶人BCL6B基因編碼序列的重組質(zhì)粒pc DNA3.1-BCL6B及其對照質(zhì)粒pc DNA3.1分別化轉(zhuǎn)至感受態(tài)大腸桿菌DH5α中,在LB培養(yǎng)基中培養(yǎng)擴增后提取質(zhì)粒,分光光度儀測定質(zhì)粒的濃度,分裝后于-20°C保存?zhèn)溆�。將擴增所得pc DNA3.1-BCL6B轉(zhuǎn)染SW480和Lo Vo細胞,經(jīng)RT-PCR、q PCR和Western blot驗證該質(zhì)粒的轉(zhuǎn)染效果。3.BCL6B對SW480和Lo Vo細胞增殖能力的影響:用pc DNA3.1-BCL6B轉(zhuǎn)染SW480和Lo Vo細胞后,經(jīng)MTT法和克隆形成試驗檢測其對細胞增殖能力的影響。4.BCL6B對SW480和Lo Vo細胞周期及凋亡的影響:用pc DNA3.1-BCL6B轉(zhuǎn)染SW480和Lo Vo細胞后,經(jīng)流式細胞術(shù)(flow cytometry,FCM)檢測和比較細胞周期及凋亡的變化。5.BCL6B對SW480和Lo Vo細胞遷移及侵襲能力的影響:用pc DNA3.1-BCL6B轉(zhuǎn)染SW480和Lo Vo細胞后,經(jīng)劃痕愈合試驗及Transwell試驗分別檢測其對細胞遷移及侵襲的影響。6.BCL6B對SW480和Lo Vo細胞中PI3K/AKT信號通路活性的影響:用pc DNA3.1-BCL6B處理SW480和Lo Vo細胞后,經(jīng)Western blot檢測細胞中p-AKT的蛋白水平;經(jīng)RT-PCR和Western blot檢測細胞中PI3K/AKT通路下游與細胞增殖及遷移相關(guān)靶基因Cyclin D1、E-cadherin和MMP-9的表達。7.PI3K/AKT信號通路在BCL6B誘導的CRC細胞增殖和遷移中的作用:聯(lián)合應(yīng)用pc DNA3.1-BCL6B和PI3K/AKT抑制劑LY294002處理Lo Vo細胞,經(jīng)MTT法和Transwell試驗分別檢測細胞增殖和遷移能力的變化;同時,經(jīng)Western blot檢測Lo Vo細胞中Cyclin D1、E-cadherin和MMP-9蛋白水平的變化。結(jié)果1.q RT-PCR結(jié)果顯示FHC、SW480和Lo Vo細胞中BCL6B的m RNA相對表達量依次為0.93±0.60、0.04±0.05和0.06±0.04。Western blot結(jié)果顯示這三株細胞中BCL6B蛋白的校正灰度值分別為0.74±0.20、0.06±0.04和0.10±0.03。即與人正常腸上皮細胞系FHC相比,BCL6B在人CRC細胞系SW480和Lo Vo中呈明顯低表達。2.pc DNA3.1-BCL6B轉(zhuǎn)染SW480和Lo Vo細胞48小時后,SW480細胞中BCL6B的m RNA和蛋白的相對灰度值分別是對照組的16.7倍(P0.01)和10.5倍(P0.01),Lo Vo細胞中BCL6B的m RNA和蛋白的相對灰度值分別是對照組的12.7倍(P0.01)和7.3倍(P0.05),提示:該重組質(zhì)粒轉(zhuǎn)染能夠上調(diào)BCL6B在CRC細胞SW480和Lo Vo中的表達,可用于后續(xù)研究。3.BCL6B抑制SW480和Lo Vo細胞的增殖能力。1)MTT檢測結(jié)果:BCL6B組SW480和Lo Vo細胞的OD值在1d及2d時與各自對照組的OD值之間無明顯差異,在3d時則分別是對照組的65.6%(P0.05)和70.7%(P0.05),在4d時分別是對照組的61.2%(P0.05)和52.7%(P0.01)。2)克隆形成試驗結(jié)果:BCL6B組SW480和Lo Vo細胞形成的克隆數(shù)分別是對照組的20.3%(P0.01)和42.2%(P0.05)。4.BCL6B可使SW480和Lo Vo細胞周期阻滯在G1期,且促進細胞凋亡。流式細胞術(shù)檢測結(jié)果:BCL6B組SW480和Lo Vo細胞G1期細胞百分比分別為對照組的1.63倍(P0.01)和1.67倍(P0.01),S期細胞百分比分別為對照組的61.1%(P0.01)和67.9%(P0.05)。同時,與對照組相比,BCL6B組SW480和Lo Vo細胞的凋亡細胞數(shù)分別增加了的0.75倍(P0.05)和2.12倍(P0.01)。5.BCL6B抑制SW480和Lo Vo細胞的遷移和侵襲能力。1)劃痕愈合試驗結(jié)果顯示,BCL6B組SW480和Lo Vo細胞48h劃痕愈合率分別為對照組的61.1%(P0.05)和55.6%(P0.05),72h劃痕愈合率分別為對照組的68.8%(P0.05)和63.9%(P0.05)。2)Transwell結(jié)果顯示,質(zhì)粒轉(zhuǎn)染后48h,對照組SW480和Lo Vo細胞的穿膜細胞數(shù)分別為177±40和143±31,BCL6B組兩種細胞的穿膜細胞數(shù)分別為69±37個和48±24,實驗組穿膜細胞數(shù)明顯低于對照組,差異具統(tǒng)計學顯著性(P0.05)。6.在pc DNA3.1-BCL6B轉(zhuǎn)染的SW480和Lo Vo細胞中:1)p-AKT較對照組分別下調(diào)67.7%(P0.05)和45.2%(P0.05)。2)SW480細胞中PI3K/AKT通路下游與增殖和遷移相關(guān)的靶基因Cyclin D1、E-cadherin和MMP-9的m RNA水平分別為對照組的63.3%(P0.05)、2.54倍(P0.05)和29.4%(P0.05),Lo Vo細胞中這三者的水平分別為對照組的32.2%(P0.01)、3.32倍(P0.05)和51.8%(P0.05);3)與之一致的是,SW480細胞中Cyclin D1、E-cadherin和MMP-9的蛋白水平分別為對照組的54.4%(P0.05)、2.05倍(P0.05)和50.6%(P0.05),Lo Vo細胞中三者的表達分別為對照組的18.9%(P0.01)、2.04倍(P0.05)和46.4%(P0.01)。以上結(jié)果提示BCL6B可通過抑制SW480和Lo Vo細胞中PI3K/AKT通路活性,進而上調(diào)E-cadherin的表達和下調(diào)Cyclin D1和MMP-9的表達,從而實現(xiàn)其抑制CRC細胞增殖和遷移的作用。7.在Lo Vo細胞中,PI3K抑制劑LY294002顯著增強了BCL6B對細胞增殖和遷移的抑制(MTT和Transwell,P0.05),同時也增強BCL6B引起的Cyclin D1和MMP-9的下調(diào)和E-cadherin的上調(diào)(P0.05)。提示PI3K/AKT信號通路的抑制參與介導BCL6B對CRC細胞增殖和遷移的抑制。結(jié)論1.BCL6B在人CRC細胞系SW480和Lo Vo中的表達明顯低于人正常腸上皮細胞系FHC。2.BCL6B抑制SW480和Lo Vo細胞的增殖、遷移和侵襲,同時促進其凋亡。3.BCL6B抑制SW480和Lo Vo細胞中PI3K/AKT通路活性,并上調(diào)E-cadherin的表達和下調(diào)Cyclin D1和MMP-9的表達。4.PI3K/AKT通路的抑制參與介導BCL6B對Lo Vo細胞增殖和遷移的抑制及對Cyclin D1、E-cadherin和MMP-9表達的調(diào)節(jié)。
[Abstract]:Background and objective Colorectal cancer (CRC) is a common digestive tract tumor. There are about 1 million new cases and 500 thousand death cases in the world each year. In China, the incidence of CRC is increasing year by year with the increase of population aging and carcinogenic factors. Now, CRC is difficult to diagnose early, and the treatment is mainly surgical excision. Migration and recurrence are still the main causes of low survival in CRC patients. Therefore, it is particularly important to elucidate the molecular mechanism of the pathogenesis of CRC, which provides a new idea for the early diagnosis, treatment and prognosis of the.B cell lymphoma 6B (B cell lymphoma 6 member B, BCL6B), which is located in the 3 band 1 subband of the short arm of human chromosome 1, and belongs to 6 of B cell lymphoma (B). Cell lymphoma 6, BCL6) a member of the superfamily, which is widely expressed in normal tissues of the human body. However, the deletion or mutation of different loci occurs in a variety of tumors; the deletion or downregulation of BCL6B expression resulting from the hypermethylation of the promoter region is commonly found in gastric cancer, liver cancer and CRC, and the degree of promoter methylation and the malignancy of the tumor and the degree of malignancy of the tumor. The poor prognosis of patients is positively correlated; in CRC, the low expression of BCL6B is associated with TNM staging, lymphatic metastasis and chemosensitivity. The increase of the expression of BCL6B in the CRC cell line activates the anti CRC effect of the p53 signaling pathway. These suggest that BCL6B may be a tumor suppressor gene. Currently, the role and mechanism of BCL6B in the tumor The purpose of this study is to detect and compare the expression level of BCL6B in human normal intestinal epithelial cell line FHC and the high metastatic potential CRC cell line SW480 and Lo Vo, to study the effect of BCL6B on the proliferation, migration and invasion of CRC cells, and to further explore its molecular mechanism, in order to clarify the role and CRC of BCL6B in the development of CRC. The mechanism accumulates the experimental basis for the development and provides new ideas for the diagnosis and treatment of CRC. Methods the endogenous expression of BCL6B in 1. normal intestinal epithelial cells and human CRC cell lines was detected by RT-PCR, Q PCR and Western blot to detect the expression of FHC and CRC cell lines in normal intestinal epithelial cell lines and CRC cell lines. The amplification and verification of the.2. recombinant plasmid PC DNA3.1-BCL6B and PC DNA3.1: the recombinant plasmid PC DNA3.1-BCL6B and its control plasmid PC DNA3.1 were transferred to the DH5 alpha of the receptive Escherichia coli respectively, and the plasmids were extracted and expanded in the medium of the LB culture, and the plasmids were determined by spectrophotometer. The effect of PC DNA3.1-BCL6B transfection on SW480 and Lo Vo cells was tested by RT-PCR, Q PCR and Western blot. The effect of the transfection of the plasmid on the proliferation ability of the plasmid was verified by RT-PCR, Q PCR and Western blot. The effect of.4.BCL6B on the cycle and apoptosis of SW480 and Lo Vo cells: the effects of PC DNA3.1-BCL6B transfection on SW480 and Lo Vo cells, through flow cytometry (flow cytometry, FCM) detection and comparison of cell cycle and apoptosis After 480 and Lo Vo cells, the effects of.6.BCL6B on the activity of PI3K/AKT signaling pathway in SW480 and Lo Vo cells were detected by scratch healing and Transwell test. The role of Cyclin D1, E-cadherin and MMP-9 signaling pathway in the proliferation and migration of CRC cells induced by BCL6B, the downstream of PI3K/AKT pathway and cell proliferation and migration related target genes,.7.PI3K/AKT signaling pathway in BCL6B induced CRC cell proliferation and migration. At the same time, the changes in the level of Cyclin D1, E-cadherin and MMP-9 protein in Lo Vo cells were detected by Western blot. The results of 1.q RT-PCR showed FHC, and the relative expression of SW480 and 0.06 + three cells showed the three cells. The corrected gray value of BCL6B protein was 0.74 + 0.20,0.06 + 0.04 and 0.10 + 0.03., respectively, compared with human normal intestinal epithelial cell line FHC, BCL6B was obviously low expression in SW480 and Lo Vo of human CRC cell line,.2.pc DNA3.1-BCL6B transfection SW480 and FHC cells were respectively the relative gray value of the protein. 16.7 times (P0.01) and 10.5 times (P0.01), the relative gray value of M RNA and protein in Lo Vo cells was 12.7 times (P0.01) and 7.3 times (P0.05) in the control group, suggesting that the recombinant plasmid transfection could up regulate the expression of BCL6B in CRC cell SW480 and the proliferation ability. .1) MTT detection results: the OD values of SW480 and Lo Vo cells in group BCL6B were not significantly different from those of the control groups at 1D and 2D, while at 3D, they were 65.6% (P0.05) and 70.7% (P0.05) in the control group, respectively, at 61.2% of the control group. The 20.3% (P0.01) and 42.2% (P0.05).4.BCL6B of the control group could block the SW480 and Lo Vo cell cycle in G1 phase and promote cell apoptosis. The percentage of SW480 and Lo Vo cells in the BCL6B group was 1.63 times as high as that of the control group and 1.67 times, respectively, and the percentage of the cells in the BCL6B group was 6 of the control group, respectively. 1.1% (P0.01) and 67.9% (P0.05). Compared with the control group, the number of apoptotic cells in the SW480 and Lo Vo cells of the BCL6B group increased by 0.75 times (P0.05) and 2.12 times (P0.01).5.BCL6B inhibition SW480 and Lo Vo cells. The healing rate of the 61.1% (P0.05) and 55.6% (P0.05) of the group was 68.8% (P0.05) and 63.9% (P0.05).2) in the control group, respectively, Transwell results showed that the number of membrane cells of the plasmid transfected 48h, SW480 and Lo Vo cells in the control group were 177 + 40 and 143 + 31 respectively. The number of membrane cells in the two cells of the BCL6B group were 69 + 37 and 48 + 24, the experimental group was dressed. The number of cells was significantly lower than that of the control group. The difference was statistically significant (P0.05).6. in SW480 and Lo Vo cells transfected by PC DNA3.1-BCL6B: 1) p-AKT decreased by 67.7% (P0.05) and 45.2% (P0.05).2), respectively. For 63.3% (P0.05), 2.54 times (P0.05) and 29.4% (P0.05) and Lo Vo cells, the levels of these three were 32.2% (P0.01), 3.32 times (P0.05) and 51.8% (P0.05) and 3) in the control group, and the Cyclin D1 in SW480 cells was 54.4% (2.05) and 50.6% (2.05 times) and 50.6% (2.05 times) and 50.6% (2.05 times), respectively, respectively. The expression of the three in the Vo cells was 18.9% (P0.01), 2.04 times (P0.05) and 46.4% (P0.01) in the control group. These results suggest that BCL6B can inhibit the PI3K/AKT pathway activity in SW480 and Lo Vo cells, and then up regulate the expression of E-cadherin and down regulation of Cyclin D1 and expression, thus realizing its inhibition of cell proliferation and migration. In o Vo cells, the PI3K inhibitor LY294002 significantly enhanced the inhibition of BCL6B on cell proliferation and migration (MTT and Transwell, P0.05), and also enhanced Cyclin D1 and MMP-9 down and up regulation of BCL6B. The expression in human CRC cell line SW480 and Lo Vo was significantly lower than that in human normal intestinal epithelial cell line FHC.2.BCL6B inhibiting the proliferation, migration and invasion of SW480 and Lo Vo cells, and promoting its apoptosis in SW480 and Lo Vo cells. Inhibition of the pathway mediates the inhibition of BCL6B on proliferation and migration of Lo Vo cells and the regulation of Cyclin D1, E-cadherin and MMP-9 expression.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.34
本文編號：2155214
[Abstract]:Background and objective Colorectal cancer (CRC) is a common digestive tract tumor. There are about 1 million new cases and 500 thousand death cases in the world each year. In China, the incidence of CRC is increasing year by year with the increase of population aging and carcinogenic factors. Now, CRC is difficult to diagnose early, and the treatment is mainly surgical excision. Migration and recurrence are still the main causes of low survival in CRC patients. Therefore, it is particularly important to elucidate the molecular mechanism of the pathogenesis of CRC, which provides a new idea for the early diagnosis, treatment and prognosis of the.B cell lymphoma 6B (B cell lymphoma 6 member B, BCL6B), which is located in the 3 band 1 subband of the short arm of human chromosome 1, and belongs to 6 of B cell lymphoma (B). Cell lymphoma 6, BCL6) a member of the superfamily, which is widely expressed in normal tissues of the human body. However, the deletion or mutation of different loci occurs in a variety of tumors; the deletion or downregulation of BCL6B expression resulting from the hypermethylation of the promoter region is commonly found in gastric cancer, liver cancer and CRC, and the degree of promoter methylation and the malignancy of the tumor and the degree of malignancy of the tumor. The poor prognosis of patients is positively correlated; in CRC, the low expression of BCL6B is associated with TNM staging, lymphatic metastasis and chemosensitivity. The increase of the expression of BCL6B in the CRC cell line activates the anti CRC effect of the p53 signaling pathway. These suggest that BCL6B may be a tumor suppressor gene. Currently, the role and mechanism of BCL6B in the tumor The purpose of this study is to detect and compare the expression level of BCL6B in human normal intestinal epithelial cell line FHC and the high metastatic potential CRC cell line SW480 and Lo Vo, to study the effect of BCL6B on the proliferation, migration and invasion of CRC cells, and to further explore its molecular mechanism, in order to clarify the role and CRC of BCL6B in the development of CRC. The mechanism accumulates the experimental basis for the development and provides new ideas for the diagnosis and treatment of CRC. Methods the endogenous expression of BCL6B in 1. normal intestinal epithelial cells and human CRC cell lines was detected by RT-PCR, Q PCR and Western blot to detect the expression of FHC and CRC cell lines in normal intestinal epithelial cell lines and CRC cell lines. The amplification and verification of the.2. recombinant plasmid PC DNA3.1-BCL6B and PC DNA3.1: the recombinant plasmid PC DNA3.1-BCL6B and its control plasmid PC DNA3.1 were transferred to the DH5 alpha of the receptive Escherichia coli respectively, and the plasmids were extracted and expanded in the medium of the LB culture, and the plasmids were determined by spectrophotometer. The effect of PC DNA3.1-BCL6B transfection on SW480 and Lo Vo cells was tested by RT-PCR, Q PCR and Western blot. The effect of the transfection of the plasmid on the proliferation ability of the plasmid was verified by RT-PCR, Q PCR and Western blot. The effect of.4.BCL6B on the cycle and apoptosis of SW480 and Lo Vo cells: the effects of PC DNA3.1-BCL6B transfection on SW480 and Lo Vo cells, through flow cytometry (flow cytometry, FCM) detection and comparison of cell cycle and apoptosis After 480 and Lo Vo cells, the effects of.6.BCL6B on the activity of PI3K/AKT signaling pathway in SW480 and Lo Vo cells were detected by scratch healing and Transwell test. The role of Cyclin D1, E-cadherin and MMP-9 signaling pathway in the proliferation and migration of CRC cells induced by BCL6B, the downstream of PI3K/AKT pathway and cell proliferation and migration related target genes,.7.PI3K/AKT signaling pathway in BCL6B induced CRC cell proliferation and migration. At the same time, the changes in the level of Cyclin D1, E-cadherin and MMP-9 protein in Lo Vo cells were detected by Western blot. The results of 1.q RT-PCR showed FHC, and the relative expression of SW480 and 0.06 + three cells showed the three cells. The corrected gray value of BCL6B protein was 0.74 + 0.20,0.06 + 0.04 and 0.10 + 0.03., respectively, compared with human normal intestinal epithelial cell line FHC, BCL6B was obviously low expression in SW480 and Lo Vo of human CRC cell line,.2.pc DNA3.1-BCL6B transfection SW480 and FHC cells were respectively the relative gray value of the protein. 16.7 times (P0.01) and 10.5 times (P0.01), the relative gray value of M RNA and protein in Lo Vo cells was 12.7 times (P0.01) and 7.3 times (P0.05) in the control group, suggesting that the recombinant plasmid transfection could up regulate the expression of BCL6B in CRC cell SW480 and the proliferation ability. .1) MTT detection results: the OD values of SW480 and Lo Vo cells in group BCL6B were not significantly different from those of the control groups at 1D and 2D, while at 3D, they were 65.6% (P0.05) and 70.7% (P0.05) in the control group, respectively, at 61.2% of the control group. The 20.3% (P0.01) and 42.2% (P0.05).4.BCL6B of the control group could block the SW480 and Lo Vo cell cycle in G1 phase and promote cell apoptosis. The percentage of SW480 and Lo Vo cells in the BCL6B group was 1.63 times as high as that of the control group and 1.67 times, respectively, and the percentage of the cells in the BCL6B group was 6 of the control group, respectively. 1.1% (P0.01) and 67.9% (P0.05). Compared with the control group, the number of apoptotic cells in the SW480 and Lo Vo cells of the BCL6B group increased by 0.75 times (P0.05) and 2.12 times (P0.01).5.BCL6B inhibition SW480 and Lo Vo cells. The healing rate of the 61.1% (P0.05) and 55.6% (P0.05) of the group was 68.8% (P0.05) and 63.9% (P0.05).2) in the control group, respectively, Transwell results showed that the number of membrane cells of the plasmid transfected 48h, SW480 and Lo Vo cells in the control group were 177 + 40 and 143 + 31 respectively. The number of membrane cells in the two cells of the BCL6B group were 69 + 37 and 48 + 24, the experimental group was dressed. The number of cells was significantly lower than that of the control group. The difference was statistically significant (P0.05).6. in SW480 and Lo Vo cells transfected by PC DNA3.1-BCL6B: 1) p-AKT decreased by 67.7% (P0.05) and 45.2% (P0.05).2), respectively. For 63.3% (P0.05), 2.54 times (P0.05) and 29.4% (P0.05) and Lo Vo cells, the levels of these three were 32.2% (P0.01), 3.32 times (P0.05) and 51.8% (P0.05) and 3) in the control group, and the Cyclin D1 in SW480 cells was 54.4% (2.05) and 50.6% (2.05 times) and 50.6% (2.05 times) and 50.6% (2.05 times), respectively, respectively. The expression of the three in the Vo cells was 18.9% (P0.01), 2.04 times (P0.05) and 46.4% (P0.01) in the control group. These results suggest that BCL6B can inhibit the PI3K/AKT pathway activity in SW480 and Lo Vo cells, and then up regulate the expression of E-cadherin and down regulation of Cyclin D1 and expression, thus realizing its inhibition of cell proliferation and migration. In o Vo cells, the PI3K inhibitor LY294002 significantly enhanced the inhibition of BCL6B on cell proliferation and migration (MTT and Transwell, P0.05), and also enhanced Cyclin D1 and MMP-9 down and up regulation of BCL6B. The expression in human CRC cell line SW480 and Lo Vo was significantly lower than that in human normal intestinal epithelial cell line FHC.2.BCL6B inhibiting the proliferation, migration and invasion of SW480 and Lo Vo cells, and promoting its apoptosis in SW480 and Lo Vo cells. Inhibition of the pathway mediates the inhibition of BCL6B on proliferation and migration of Lo Vo cells and the regulation of Cyclin D1, E-cadherin and MMP-9 expression.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.34
【參考文獻】
相關(guān)期刊論文 前1條
1 李道娟;李倩;賀宇彤;;結(jié)直腸癌流行病學趨勢[J];腫瘤防治研究;2015年03期
，本文編號：2155214
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