白藜芦醇在妇科肿瘤中的研究进展

白藜芦醇是在葡萄等植物中广泛存在的多酚类化合物,研究表明,白藜芦醇可以通过抗氧化、抑制环氧化酶、抑制癌细胞增殖、诱导癌细胞分化和凋亡等作用机制参与抑制宫颈癌、卵巢癌、子宫内膜癌等妇科肿瘤生长的过程。     

植物化学物复方抗癌实验研究

目的 研究人参皂苷、白藜芦醇、灵芝多糖及冬虫夏草四种植物化学物单药其及复方的体外抗癌活性,探讨四种 植物化学物联合使用是否具有协同抗癌作用。方法 体外培养A549、MCF-7、SW480三株癌细胞,CCK8法检测人参皂苷、 白藜芦醇、灵芝多糖、冬虫夏草单药及其复方对三株癌细胞生长抑制率的影响;流式细胞仪检测分析植物化学物GRGC 复 方阻滞癌细胞周期及诱导癌细胞凋亡的作用;透射电镜观察植物化学物GRGC复方诱导A549肺癌细胞凋亡的形态学变化。 结果 人参皂苷、白藜芦醇、灵芝多糖及冬虫夏草对A549、MCF-7、SW480 三株癌细胞均具有显著的抑制杀伤作用,并随 药物浓度的增加其杀伤活性更强,呈明显剂量效应关系。人参皂苷、白藜芦醇、灵芝多糖、冬虫夏草配制成复方联合用药时, 其杀伤效应较单药显著增强,有明显的协同抗癌效应。流式细胞周期分析显示植物化学物GRGC 复方能将A549、MCF7、SW480 三株癌细胞周期阻滞于G0/G1 期。流式细胞凋亡分析GRGC 复方诱导A549、MCF-7、SW480 三株癌细胞凋亡 呈剂量依赖性。在透射电镜下可观察到GRGC 复方能诱导A549 癌细胞细胞膜破损、核被膜消失、胞核逐渐浓缩聚集成新 月状或形成凋亡小体。结论 人参皂苷、白藜芦醇、灵芝多糖、冬虫夏草 GRGC 复方对体外培养的 A549、MCF-7、SW480 三株癌细胞的抑制杀伤效率比单药显著增强,具有明显的协同抗癌效应,能阻滞A549、MCF-7 和 SW480 癌细胞周期于 G0/G1 期,阻滞癌细胞增殖,并能有效诱导 A549、MCF-7、SW480 癌细胞凋亡,抑制癌细胞的生长 , 为肿瘤的综合治疗打 下坚实的基础。     

白藜芦醇对胃癌细胞HGC27细胞周期的影响

目的：研究白藜芦醇对胃癌细胞株HGC27细胞细胞周期的影响。方法：不同浓度的白藜芦醇作用于HGC27细胞,用流式细胞术分析细胞周期。结果：白藜芦醇作用后,HGC27细胞的增殖速度减缓,DNA合成减少。白藜芦醇在较低浓度时即可诱导G0／G1阻滞。结论：白藜芦醇可诱导胃癌细胞发生G0／G1阻滞,S期减少。     

白藜芦醇对胃癌细胞HGC27细胞周期的影响

目的:研究白藜芦醇对胃癌细胞株HGC27细胞细胞周期的影响.方法:不同浓度的白藜芦醇作用于HGC27细胞,用流式细胞术分析细胞周期.结果:白藜芦醇作用后,HGC27细胞的增殖速度减缓,DNA合成减少.白藜芦醇在较低浓度时即可诱导G0/G1阻滞.结论:白藜芦醇可诱导胃癌细胞发生G0/G1阻滞,S期减少.     

Salubrinal抑制射线诱导NF-κB活化增加口腔癌细胞凋亡

目的 探讨Salubrinal调控射线诱导口腔癌细胞凋亡的作用机制。方法 构建放射抗拒口腔癌细胞KBR (4 Gy/次,7~10d 1次共4次);克隆形成实验检测Salubrinal预处理后口腔癌细胞放射敏感性;蛋白印迹法检测射线及Salubrinal调控口腔癌细胞NF-κB-HIF-1α信号通路及凋亡标志蛋白cleaved PARP的表达;Annexin V、PI染色、流式细胞仪检测凋亡分数。结果 克隆形成实验示Salubrinal增加口腔癌细胞放射敏感性,KB及KBR细胞放射增敏比分别为1.19和1.24。蛋白印迹法结果示射线诱导口腔癌细胞NF-κB-HIF-1α细胞活化具有时间依赖性,而Salubrinal抑制射线诱导其异常活化。Salubrinal增加射线诱导口腔癌细胞凋亡标志蛋白cleaved PARP表达及凋亡指数,而NF-κB激活剂TNF-α逆转了这一作用,提示Salubrinal通过抑制NF-κB活化增加射线调控口腔癌细胞凋亡。进一步应用NF-κB抑制剂Bay11-7082同样增加射线诱导口腔癌细胞凋亡,KB及KBR细胞系Bay11-7082+IR组cleaved PARP的表达为2.67±0.26、1.91±0.17,IR组为2.1±0.16、1.44±0.15(P<0.05)。结论 Salubrinal抑制射线诱导NF-κB活化增加射线诱导口腔癌细胞凋亡进而调控口腔癌细胞放射敏感性。     

Salubrinal抑制射线诱导NF-κB活化增加口腔癌细胞凋亡

目的 探讨Salubrinal调控射线诱导口腔癌细胞凋亡的作用机制。方法 构建放射抗拒口腔癌细胞KBR (4 Gy/次,7~10d 1次共4次);克隆形成实验检测Salubrinal预处理后口腔癌细胞放射敏感性;蛋白印迹法检测射线及Salubrinal调控口腔癌细胞NF-κB-HIF-1α信号通路及凋亡标志蛋白cleaved PARP的表达;Annexin V、PI染色、流式细胞仪检测凋亡分数。结果 克隆形成实验示Salubrinal增加口腔癌细胞放射敏感性,KB及KBR细胞放射增敏比分别为1.19和1.24。蛋白印迹法结果示射线诱导口腔癌细胞NF-κB-HIF-1α细胞活化具有时间依赖性,而Salubrinal抑制射线诱导其异常活化。Salubrinal增加射线诱导口腔癌细胞凋亡标志蛋白cleaved PARP表达及凋亡指数,而NF-κB激活剂TNF-α逆转了这一作用,提示Salubrinal通过抑制NF-κB活化增加射线调控口腔癌细胞凋亡。进一步应用NF-κB抑制剂Bay11-7082同样增加射线诱导口腔癌细胞凋亡,KB及KBR细胞系Bay11-7082+IR组cleaved PARP的表达为2.67±0.26、1.91±0.17,IR组为2.1±0.16、1.44±0.15(P<0.05)。结论 Salubrinal抑制射线诱导NF-κB活化增加射线诱导口腔癌细胞凋亡进而调控口腔癌细胞放射敏感性。     

荧光染料Hoechst 33342与细胞凋亡

荧光染料Hoechest33342在计数细胞周期及细胞凋亡研究方面得到广泛的应用。研究发现,Hoeehst33342可诱导如BC3H—1细胞、HL-60细胞、HT-144黑色素瘤细胞、肝细胞癌细胞等多种细胞凋亡。Hoeehest33342对拓扑异构酶I活性的抑制、对TATA盒结合蛋白的抑制、细胞内E2F-1蛋白表达的增加和线粒体功能不良可能是其诱导细胞凋亡的主要机制。     

白藜芦醇靶向EGFR和c-Met信号通路抑制非小细胞肺癌细胞增殖的机制

 目的 探讨白藜芦醇抑制非小细胞肺癌细胞增殖的分子机制。方法 非小细胞肺癌细胞用白藜芦醇处理24、48和72 h,MTS和软琼脂集落形成实验检测白藜芦醇对非小细胞肺癌的抑制作用,免疫印迹检测白藜芦醇对表皮生长因子受体（epidermal growth factor receptor, EGFR）和肝细胞生长因子受体（c-Met）表达水平及下游信号通路的影响,流式细胞术检测白藜芦醇对细胞周期的影响。结果 白藜芦醇剂量依赖性抑制非小细胞肺癌细胞的增殖。白藜芦醇抑制EGFR和c-Met信号通路磷酸化活化的同时下调了EGFR总蛋白及EGFR在胞膜和胞核的表达,同时降低了c-Met蛋白在胞膜的表达及c-Met蛋白60 kD大小剪切体在胞核的表达。白藜芦醇促进了A549细胞G₀/G₁期阻滞。结论 白藜芦醇通过靶向EGFR和c-Met信号通路抑制非小细胞肺癌细胞的增殖。     

白藜芦醇抑制EGF诱导人肺腺癌A549细胞侵袭

背景与目的侵袭转移是人肺腺癌死亡的主要原因,表皮生长因子(epidermal growth factor,EGF)可通过活化ERK和PI3K-Akt信号通路,促进人肺腺癌A549细胞侵袭。本实验旨在研究白藜芦醇抑制EGF诱导体外A549细胞侵袭的作用,并初步探讨其机制。方法采用MTT法确定白藜芦醇对A549细胞无明显毒性的浓度范围,并以该浓度范围内的白藜芦醇作用EGF诱导的A549细胞,Transwell小室法检测其抑制细胞侵袭作用,明胶酶谱法分析细胞的MMP-2活性变化,Westernblot检测EGF信号通路相关蛋白表达。结果30μM内的白藜芦醇无明显的细胞毒性,20μM处理的受EGF诱导的A549细胞侵袭能力明显降低,MMP-2分泌减少,胞内p-ERK1/2和PI3K(0.5h-6h)含量下降。结论20μM白藜芦醇可有效抑制A549细胞侵袭,其机制可能是通过抑制ERK通路和PI3K-Akt通路中相关蛋白激活,最终降低MMP-2的分泌。     

n-3多不饱和脂肪酸在食管癌细胞增殖和凋亡中的作用机制探讨

目的:探讨n-3多不饱和脂肪酸的两个活性成分二十二碳六烯酸(DHA)和二十碳五烯酸(EPA)在食管癌细胞增殖和凋亡中的作用。方法:采用 CCK-8法测定不同浓度、不同时间点（培养后 24 h、48 h、72 h）的DHA、EPA对食管癌细胞增殖的影响,用Western-blot法检测DHA、EPA对凋亡相关蛋白表达的影响,并用荧光染色和流式细胞仪检测DHA、EPA对食管癌细胞凋亡的影响。结果:与对照组相比,DHA和EPA均能够抑制食管癌细胞的增殖并具浓度依赖性,但无时间依赖性。Western-blot 显示DHA、EPA能激活Caspase-3和Bax表达,抑制抗凋亡蛋白Bcl-2表达。DHA和EPA作用24 h后,荧光染色可见部分食管癌细胞呈典型的凋亡形态学改变。流式细胞仪检测结果显示,与对照组比较,DHA和EPA能够诱导食管癌细胞凋亡,且与浓度呈正比。结论:n-3多不饱和脂肪酸能够抑制食管癌细胞的增殖和诱导食管癌细胞的凋亡,调控Caspase-3活性以及 Bcl-2 家族促凋亡蛋白/抗凋亡蛋白之间的平衡来发挥其抑制食管癌细胞增殖和诱导食管癌细胞凋亡的作用。     

A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol

Resveratrol, a phytoalexin found in grapes and wines, has been reported to exhibit a wide range of pharmacological properties and is believed to play a role in the prevention of human cardiovascular disease (the so-called 'French paradox'). This molecule may also play a major role in both cancer prevention and therapy. In this review article we summarize the recent advances that have provided new insights into the molecular mechanisms underlying the promising properties of resveratrol. These include cyclooxygenase, nitric oxide synthase and cytochrome P450 inhibition, as well as cell cycle effects, apoptosis modulation and hormonal activity.     

Resveratrol induces DNA double-strand breaks through human topoisomerase II interaction

Resveratrol, a stilbene found in grapes and wine, is one of the most interesting natural compound due to its role exerted in cancer prevention and therapy. In particular, resveratrol is able to delay cell cycle progression and to induce apoptotic death in several cell lines. Here we report that resveratrol treatment of human glioblastoma cells induces a delay in cell cycle progression during S phase associated with an increase in histone H2AX phosphorylation. Furthermore, with an in vitro assay of topoisomerase IIα catalytic activity we show that resveratrol is able to inhibit the ability of recombinant human TOPO IIα to decatenate kDNA, so that it could be considered a TOPO II poison.     

Resveratrol and estradiol exert disparate effects on cell migration, cell surface actin structures, and focal adhesion assembly in MDA-MB-231 human breast cancer cells

Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2), or epidermal growth factor (EGF) was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK) activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.     

白藜芦醇与癌的化学预防

白藜芦醇,又名3,5,4′-三羟基反苯二烯,是一种存在于葡萄及其他一些天然产物中的多酚类化合物.白藜芦醇在癌症的始发、促进及发展阶段均表现出显著的抑制作用,因此它被认为是极有希望成为癌症的化学预防药物.本文就白藜芦醇在癌的化学预防方面的作用,包括抗氧化、抗突变、抗促癌、调控细胞周期、诱导凋亡和激素调节等作用及其机制做一综述.     

Resveratrol-mediated ADAM9 degradation decreases cancer progression and provides synergistic effects in combination with chemotherapy

Metastasis is a crucial hallmark of cancer progression and remains the primary cause of patient deaths. Metastasis-associated proteases contribute to cancer progression by disrupting the extracellular matrix interaction to facilitate the spreading of cancer cells to other organs. ADAM9, a type of metalloprotease, has been reported to promote tumor biology and is associated with clinicopathological features such as poor outcome, therapy resistance, and metastasis formation. Targeting ADAM9 might serve as a putative therapeutic application; however, this option is currently unavailable. Resveratrol, a polyphenol from plants, has been shown to be promising for cancer treatment due to its wide variety of biological effects with few side effects. In this study, we demonstrated that resveratrol inhibits cancer cell migration and viability in lung and esophageal cancer cells through the regulation of ADAM9. Mechanistically, resveratrol inhibits ADAM9 protein expression in cancer cells through the ubiquitin-proteasome pathway. Moreover, resveratrol provides synergistic anticancer effects when combined with clinical chemotherapeutics. Our data suggests that resveratrol may inhibit human lung cancer and ESCC progression by inhibiting ADAM9 expression, thus providing a potential mechanism for the anticancer action of resveratrol.     

Role of Resveratrol as Radiosensitizer by Targeting Cancer Stem Cells in Radioresistant Prostate Cancer Cells (PC-3)

Aim of Work: Here, we examined the role of resveratrol as a radiosensitizer by targeting cancer stem cells in radioresistant prostate cancer cells (PC-3) using stem cell markers CD44, CD49b and CD29, SOX2, OCT4, CXCR4, DCLK1 and EMT markers such as VIM and E-cadherin. Material and Methods: This study was an in vitro study involving PC-3 cell line which was dividing into four groups. Group I (CO): Control group composed of cells grown in the same medium without treatment with ionizing radiation or resveratrol. Group II (IR): Cells were treated with ionizing radiation alone. Group III (RV): Cells were treated with resveratrol alone. Group VI (IR&RV): The cells were treated with ionizing radiation and resveratrol in combination. The viability of cells was assessed by MTT assay. Genes of interest were measured by RT-PCR and the radiosensitizing efficacy of RV on proliferating cancer cells was determined by clonogenic assay. Results: Ionizing radiation significantly reduced PC-3 viability, lowered stem cell markers and affected epithelial to mesenchymal transition (EMT) genes expression at all doses (2, 4, 6 and 8 Gray). Resveratrol significantly decreased PC-3 viability and lowered stem cell markers and EMT genes expression at concentrations 35, 70 and 140 µM. Combining resveratrol treatment with ionizing radiation leads to significant reduction in cell viability and stem cell markers genes which was noticed with increasing the radiation dose when compared to ionizing radiation alone treated group. Conclusion: Resveratrol has a radiosensitizing effect, that ability is triggered by reducing the expression of cancer stem cell markers and affecting EMT markers. Resveratrol showed to be a good candidate for further studies as anticancer drug in the treatment of human prostate cancer.     

Genome-scale analysis of resveratrol-induced gene expression profile in human ovarian cancer cells using a cDNA microarray

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural compound found in large quantities, most notably in grapes and red wine, which has been shown to have anti-inflammatory, chemopreventive and anti-angiogenic effects. We examined whether resveratrol has any effect on growth and gene expression in the human ovarian cancer PA-1 cells. We show that resveratrol inhibits cell growth and induces apoptosis in PA-1 human ovarian cancer cells. We also investigated the effect of resveratrol on changes of global gene expression during resveratrol-induced growth inhibition and apoptosis in PA-1 cells using a human cDNA microarray with 7,448 sequence-verified clones. Out of the 7,448 genes screened, 118 genes were founded to be affected in their expression levels by more than 2-fold after 24-h treatment with 50 micro M resveratrol. Resveratrol treatment of PA-1 cells at the final concentration of 50 micro M for 6, 12, 24 and 48 h and gene expression patterns were analyzed by microarray. Clustering of the genes modulated more than 2-fold at three of the above times points divided the genes into 2 groups. Within these groups, there were specific subgroups of genes whose expressions were substantially changed at the specified time points. One of the most highly up-regulated genes found in this study was NAD(P)H quinone oxidoreductase 1(NQO-1), which has recently been shown to be involved in p53 regulation. Although the precise roles of genes whose expression levels were found to fluctuate after resveratrol treatment remain to be elucidated, we hope that the new view of gene expression in human ovarian cancer cells following resveratrol exposure, as offered by this study, provides clues for the mechanism of resveratrol action.