Ephrin B2上调促进非小细胞肺癌上皮间质转化及转移

目的:探究Ephrin B2上调对非小细胞肺癌(NSCLC)上皮间质转化及转移的影响。方法:选取NSCLC组织和癌旁正常肺组织,免疫组织化学方法检测NSCLC和正常组织中Ephrin B2蛋白阳性表达率。将转染后的细胞分为4组:空白组(Blank组)、阴性对照组(NC组)、Ephrin B2 vector组、sh-Ephrin B2组。qRT-PCR和Western blot检测各组细胞Ephrin B2、Ecadherin、N-cadherin、Vimentin、MMP-2的表达水平。划痕实验检测各组转染后细胞迁移能力。结果:NSCLC组织中Ephrin B2蛋白表达显著高于正常肺组织和癌旁组织(P <0. 05)。与Blank组相比,Ephrin B2 vector组细胞迁移能力上升,Ephrin B2、Ncadherin、Vimentin、MMP-2 mRNA表达上升(P <0. 05),E-cadherin mRNA和蛋白表达水平下降(P <0. 05)。sh-Ephrin B2组细胞迁移能力下降,Ephrin B2、N-cadherin、Vimentin、MMP-2 mRNA和蛋白表达水平下降(P <0. 05),E-cadherin mRNA和蛋白表达水平上升(P <0. 05)。结论:Ephrin B2上调促进非小细胞肺癌上皮间质转化及转移。

EGFR/EGFRvⅢ促头颈肿瘤上皮-间质转移的研究

表皮生长因子受体(EGFR)属受体酪氨酸激酶生长因子受体家族,由原癌基因erb B1编码并翻译的蛋白。表皮生长因子受体三型突变(EGFRvⅢ)是EGFR的一种最常见突变体,EGFR和EGFRvⅢ在头颈肿瘤中广泛表达。其与相应的配体结合后主要通过Ras/Raf/丝裂原激活蛋白激酶的激酶/细胞外信号调节激酶/丝裂原活化蛋白激酶和磷脂酰肌醇3-激酶/蛋白激酶B信号通路,促进肿瘤细胞生长、调节细胞周期、诱导血管形成、加速肿瘤侵袭和转移、拮抗放、化疗效果,从而影响肿瘤的预后。

T-钙黏蛋白与恶性胶质瘤发生、发展及放疗敏感性的关系

目的探讨T-钙黏蛋白与恶性胶质瘤发生、发展及放疗敏感性的关系。方法(1)取37例恶性胶质瘤患者的癌组织和癌旁组织,以及正常胶质细胞株HEB和胶质瘤细胞系U251、A172,检测其T-钙黏蛋白mRNA和蛋白的表达情况。比较不同T-钙黏蛋白表达情况的患者的中位生存期。(2)将U251细胞、A172细胞分别分为空白对照组、阴性对照组、T-钙黏蛋白过表达组,空白对照组细胞不进行转染,将质粒pcDNA3.1、pcDNA3.1-T-cadherin分别转染至阴性对照组、T-钙黏蛋白过表达组细胞。检测转染后各组U251、A172细胞的增殖、凋亡、迁移能力,T-钙黏蛋白、波形蛋白、E-钙黏蛋白的表达水平。对转染后各组U251、A172细胞进行放射干预后,检测细胞存活率和相对克隆数。将各组转染后的U251细胞皮下注射至裸鼠右侧腋窝处,观察注射部位的成瘤情况。结果(1)恶性胶质瘤组织中T-钙黏蛋白的mRNA表达水平和阳性表达率均低于癌旁组织;T-钙黏蛋白表达阴性患者中位生存期短于T-钙黏蛋白表达阳性患者(均P<0.05)。与正常胶质细胞株HEB相比,胶质瘤细胞系U251和A172中T-钙黏蛋白的mRNA和蛋白表达水平均下调(均P<0.05)。(2)与空白对照组、阴性对照组比较,T-钙黏蛋白过表达组U251与A172细胞的EdU阳性率均降低,细胞凋亡率升高,迁移细胞数减少,波形蛋白表达水平下调,而T-钙黏蛋白和E-钙黏蛋白表达水平均上调,4 Gy、6 Gy的γ射线照射后细胞存活率降低,6 Gy的γ射线照射后细胞相对克隆数减少(均P<0.05)。与空白对照组、阴性对照组比较,T-钙黏蛋白过表达组裸鼠的肿瘤体积缩小(均P<0.05)。结论T-钙黏蛋白在恶性胶质瘤中呈现异常低表达状态。过表达T-钙黏蛋白能够明显抑制恶性胶质瘤的发展,并提高其放疗敏感性,有利于改善患者预后。

Eph 蛋白在卵巢癌中的研究进展

Eph 蛋白是酪氨酸激酶受体中最大的受体家族，能够通过与血管内皮生长因子相互作用、调控肿瘤细胞上皮间质转移的发生等方式，影响肿瘤的新生血管形成和侵袭转移。国内外研究发现，在卵巢癌组织中存在多种 Eph 蛋白的表达异常。随着进一步研究，将 Eph 蛋白作为肿瘤治疗的靶目标，改变肿瘤中 Eph 蛋白的表达可能成为肿瘤靶向治疗的新方法。

Cullin 4A is associated with epithelial to mesenchymal transition and poor prognosis in perihilar cholangiocarcinoma

AIM To explore the functional role of cullin 4A(CUL4A), a core subunit of E3 ubiquitin ligase, in perihilar cholangiocarcinoma(PHCC).METHODS The expression of CUL4 A in PHCC cell lines was evaluated by Western blot and quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry(IHC) was adopted to investigate the relationship between CUL4 A expression and clinicopathological characteristics of PHCC. Univariate analysis and multivariate regression analysis were performed to analyze the risk factors related to overall survival(OS) and progression-free survival(PFS) of PHCC patients. Wound healing, Transwell and Matrigel assays were utilized to explore the function of CUL4 A in PHCC metastasis. Furthermore, expression of epithelial to mesenchymal transition(EMT) markers was verified in cells with CUL4 A knockdown or overexpression. The relationship between CUL4 A expression and E-cadherin expression was also analyzed by IHC assay. Finally, the role of ZEB1 in regulating CUL4 A mediated PHCC was detected by IHC, Western blot, Transwell and Matrigel assays.RESULTS CUL4 A overexpression was detected in PHCC cell lines and clinical specimens. Clinicopathological analysis revealed a close correlation between CUL4 A overexpression and tumour differentiation, T, N and TNM stages in PHCC. Kaplan-Meier analysis revealed that high CUL4 A expression was correlated with poor OS and PFS of PHCC patients. Univariate analysis identified the following four parameters as risk factors related to OS rate of PHCC: T, N, TNM stages and high CUL4 A expression; as well as three related to PFS: N stage, TNM stage and high CUL4 A expression. Further multivariate logistic regression analysis identified high CUL4 A expression as the only independent prognostic factor for PHCC. Moreover, CUL4 A silencing in PHCC cell lines dramatically inhibited metastasis and the EMT. Conversely, CUL4 A overexpression promoted these processes. Mechanistically, ZEB1 was discovered to regulate the function of CUL4 A in promoting the EMT and metastasis.CONCLUSION CUL4 A is an independent prognostic factor for PHCC, and it can promote the EMT by regulating ZEB1 expression. CUL4 A may be a potential therapeutic target for PHCC.

Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition

Objective: Drug-resistance and metastasis are major reasons for the high mortality of ovarian cancer(OC) patients. Cyclooxygenase-2(COX-2) plays a critical role in OC development. This study was designed to evaluate the effects of COX-2 on migration and cisplatin(cis-dichloro diammine platinum, CDDP) resistance of OC cells and explore its related mechanisms. Methods: Cell counting kit-8(CCK-8) assay was used to detect the cytotoxicity effects of celecoxib(CXB) and CDDP on SKOV3 and ES2 cells. The effect of COX-2 on migration was evaluated via the healing test. Western blot and real-time quantitative polymerase chain reaction(q PCR) were used to analyze E-cadherin, vimentin, Snail, and Slug levels. Results: COX-2 promoted drug-resistance and cell migration. CXB inhibited these effects. The combination of CDDP and CXB increased tumor cell sensitivity, reduced the amount of CDDP required, and shortened treatment administration time. COX-2 upregulation increased the expression of Snail and Slug, resulting in E-cadherin expression downregulation and vimentin upregulation. Conclusions: COX-2 promotes cancer cell migration and CDDP resistance and may serve as a potential target for curing OC.