自噬在肿瘤发生与发展中的调控机制

自噬是一个多步骤的动态过程,包括诱导、成核、延伸、自噬体形成、自噬溶酶体形成,细胞将自身胞浆蛋白或细胞器包裹形成囊泡并在溶酶体中降解,在维持细胞内稳态中发挥重要的作用。多种肿瘤细胞中存在自噬活性的改变,参与细胞恶变及肿瘤细胞生长。在肿瘤发生早期,细胞利用自噬清除细胞内折叠异常的蛋白质和功能异常的细胞器如线粒体,抑制细胞应激反应,防止基因损伤从而抑制肿瘤发生。在肿瘤发展过程中,肿瘤细胞利用自噬作用帮助自身在营养缺乏和低氧状况下得以存活。研究自噬在肿瘤发生发展中的调控机制将为肿瘤治疗提供新策略。     

自噬与肿瘤干细胞的研究进展

细胞自噬是以细胞质空泡化为特征的溶酶体依赖性降解途径,对维持细胞内环境稳定有重要意义,异常自噬与肿瘤发生密切相关.肿瘤干细胞是存在于肿瘤组织中一类数量较少但具有干细胞特性的肿瘤细胞,可诱导肿瘤发生并对肿瘤的发展、转移、复发起重要作用.肿瘤干细胞中自噬的调节已成为研究热点,将为肿瘤的临床治疗提供新的理论依据.     

自噬相关基因ATG5在肿瘤发生发展及治疗中的作用

摘 要：自噬是细胞质大分子或细胞器在溶酶体中降解以维持细胞平衡的过程,在肿瘤的生物学中起着重要作用。自噬相关基因5(autophagy-related gene 5,ATG5)是自噬体形成关键调控者之一,近年来,许多研究报道ATG5在多种肿瘤中的表达不尽相同,对肿瘤的影响也并不一致。文章就ATG5在肿瘤发生发展及治疗和预后中的作用作一综述。     

自噬与肿瘤化疗耐药关系的研究进展

自噬是一种自我降解的细胞过程,主要负责降解功能失调或不必要的蛋白质和细胞器,以维持细胞内稳态。近年来,肿瘤与自噬的关系一直颇受关注,越来越多的证据表明自噬在肿瘤发生发展及治疗中具有自相矛盾的作用。化疗是目前治疗癌症最有效的方法之一,与手术、放疗并称为癌症的三大治疗手段。但化疗过程中产生的获得性耐药已成为肿瘤治疗失败的首要原因。有研究表明,自噬是肿瘤化疗耐药的关键过程之一。本文就自噬与肿瘤化疗耐药的相关性及研究进展进行综述。     

妇科常见肿瘤中细胞自噬现象的研究进展

目的:总结妇科常见肿瘤中细胞自噬现象的研究进展。方法:以"Autoph-agy"、"Beclin1"和"肿瘤"为关键词,检索2006-2010 PubMed及CNKI期刊全文数据库。纳入标准:1)细胞自噬与妇科肿瘤发生发展的关系;2)自噬相关基因Beclin1的结构及生物学特性;3)细胞自噬与妇科肿瘤的治疗。根据纳入标准分析28篇文献。结果:细胞自噬对肿瘤发生发展具有促进与抑制双重作用。卵巢癌、子宫内膜癌及宫颈癌等常见妇科恶性肿瘤组织中都存在自噬活性降低的现象。Beclin1在自噬活性缺失的妇科恶性肿瘤形成中起到了关键的作用,它可提高肿瘤细胞的自噬与凋亡能力并抑制肿瘤的恶性增殖。多种抗癌药物均可通过诱导细胞自噬而造成肿瘤细胞的死亡。细胞自噬及Beclin1基因为妇科肿瘤的治疗提供了一种新思路。结论:通过抑制具有细胞保护效应的自噬反应或促进可诱导凋亡的细胞自噬有可能成为妇科肿瘤生物治疗中的重要靶点。     

自体吞噬在肿瘤发展中的作用及其与肿瘤治疗

自体吞噬是一种在正常细胞和病态细胞中普遍存在的生理机制,对于维持细胞内蛋白质平衡,清除细胞内受损细胞器维持内环境稳定起关键作用.自噬在肿瘤不同发展阶段具有促进或抑制肿瘤两方面的作用,通过药物改变肿瘤细胞的自噬程度对于治疗肿瘤有着潜在的应用前景.     

自噬与肿瘤的关系

在某些条件下,自噬能保护肿瘤细胞免受杀伤,而在另外的环境下自噬又具有抗肿瘤作用.在抗肿瘤药应用方面,自噬诱导细胞死亡的机制也存在很大争议.在肿瘤发生发展过程中,自噬扮演着不同角色,在不同阶段促进或抑制肿瘤生长.     

自噬在胃肠道肿瘤的研究

自噬是由溶酶体介导的细胞降解程序,参与维持细胞稳定.在胃肠道肿瘤早期阶段,自噬清除毒性损伤以对抗肿瘤进展;而肿瘤进展期则呈现细胞杀伤与细胞保护的两面性.在自噬与细胞凋亡之间亦存在拮抗与协同的双重作用.合理调控自噬有可能成为胃肠道肿瘤预防或治疗的一种新手段.     

细胞自噬在肿瘤中的作用

自噬为一种细胞的自我消耗过程,其具有潜在的抗肿瘤生物学活性,亦与肿瘤耐药有关.该文从自噬的调节机制入手,综述自噬参与肿瘤发生的机制,自噬在肿瘤治疗中的作用及应用,以期为自噬在临床上的应用提供依据.     

自噬在恶性肿瘤治疗中的进展及影像学应用前景

自噬是在营养缺乏条件下维持细胞代谢的主要途径。这使其成为肿瘤研究的新热点,调控自噬信号通路的机制已经很明确,越来越多的研究发现机体细胞自噬活性变化对肿瘤治疗的效果具有巨大影响。但缺乏能够重复比较或靶向定位自噬活性的测量技术。正电子示踪剂PET等影像手段通过将相关自噬的信号通路蛋白标记放射性核素进行显像似乎具有解决这些问题的潜力。在本文中,我们综述自噬在肿瘤治疗中的应用,并展望医学影像技术协助自噬治疗肿瘤的前景。     

Autophagy and cancer: Basic mechanisms and inhibitor development

Autophagy is a lysosomal degradation system of cytoplasmic components that contributes to cellular homeostasis through the turnover of various biomolecules and organelles, often in a selective manner. Autophagy is closely related to cancer, but its roles in cancer are complicated. It works as either a promoter or suppressor, depending on the stage and type of cancer. In this review, we briefly summarize the basic mechanisms of autophagy and describe the complicated roles of autophagy in cancer. Moreover, we summarize the clinical trials of autophagy inhibitors targeting cancer and the development of more specific autophagy inhibitors for future clinical application.     

自噬在前列腺癌发生发展和治疗中的研究进展

自噬是真核细胞通过溶酶体对其自身生物大分子和细胞器回收再利用的过程,其在维持细胞稳态中发挥重要作用,并参与多种病理生理过程。在肿瘤的发病过程中,自噬发挥“双面作用”,既可以抗癌也能促癌。前列腺癌是老年男性最常见的恶性肿瘤,研究表明前列腺癌的发生发展与自噬作用密切相关,放化疗、内分泌治疗等对肿瘤细胞造成的应激可通过自噬得以缓解,抵抗治疗,因而自噬抑制剂对于放化疗等具有协同促进作用。本文就自噬在前列腺癌中发病和治疗进行综述,以期为前列腺癌的诊治提供一些新的思路。     

Autophagy as a therapeutic target in cancer

Autophagy is a self-catabolic process that maintains intracellular homeostasis and prolongs cell survival under stress via lysosomal degradation of cytoplasmic constituents and recycling of amino acids and energy. Autophagy is intricately involved in many aspects of human health and disease, including cancer. Autophagy is a double-edged sword in tumorigenesis, acting both as a tumor suppressor and a protector of cancer cell survival, and elucidation of its exact role at different stages of cancer progression and in treatment responsiveness is a complex and challenging task. Better understanding of autophagy regulation and its impact on treatment outcome will potentially allow us to identify novel therapeutic targets in cancer. In this review, we summarize current knowledge on the regulation and dual function of autophagy in tumorigenesis, as well as ongoing efforts in modulating autophagy for cancer treatment and prevention. This is a very exciting and highly promising area of cancer research, as pharmacologic modulation of autophagy appears to augment the efficacy of currently available anticancer regimens and opens the way to the development of new combinatorial therapeutic strategies that will hopefully contribute to cancer eradication.     

Autophagy and multidrug resistance in cancer

Multidrug resistance (MDR) occurs frequently after long-term chemotherapy,resulting in refractory cancer and tumor recurrence.Therefore,combatting MDR is an important issue.Autophagy,a self-degradative system,universally arises during the treatment of sensitive and MDR cancer.Autophagy can be a double-edged sword for MDR tumors:it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive.Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells,facilitating MDR reversal.Therefore,research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important.We summarize advanced studies of autophagy in MDR tumors,including the variable role of autophagy in MDR cancer cells.     

Autophagy is needed for the growth of pancreatic adenocarcinoma and has a cytoprotective effect against anticancer drugs

Background and aimAutophagy is a regulated process of degradation and recycling of cellular constituents. The role of autophagy in pancreatic cancer is still not clear. Some studies indicate that in pancreatic cancer autophagy exerts cytoprotective effects, whereas others suggest that autophagy positively contributes to cell death by enhancing cytotoxicity of anticancer drugs. The aim of this study was to investigate the role of autophagy in pancreatic cancer, and to provide insights into new strategies for treatment.Materials and methodsPancreatic cancer cell lines PANC-1 and BxPC-3 were treated with anticancer drugs (5-fluorouracil or gemcitabine) alone and in combination with autophagy inhibitors (chloroquine or wortmannin). Biopsy samples were retrieved from patients from pancreatic normal tissue and adenocarcinoma. Western blot of microtubule-associated protein 1 light chain 3 (LC3)-II was performed to investigate the degree of autophagy and cell proliferation was assessed by a crystal violet assay.ResultsAutophagy was active in PANC-1 cells under basal conditions. Autophagy was significantly induced in pancreatic ductal adenocarcinoma compared to healthy pancreatic tissue in patients. Inhibition of autophagy by chloroquine suppressed the growth of PANC-1 and BxPC-3. Autophagy was markedly increased after treatment with 5-fluorouracil or gemcitabine. Inhibition of autophagy by chloroquine potentiated the inhibition of cell proliferation of PANC-1 and BxPC-3 by 5-fluorouracil and gemcitabine.ConclusionsOur results with pancreatic cancer cell lines and human pancreatic adenocarcinoma suggest that autophagy contributes to pancreatic cancer cell growth. Autophagy has a cytoprotective effect against 5-fluorouracil and gemcitabine in pancreatic cancer cells. Combination therapy of these anticancer drugs and chloroquine should be investigated.     

宫颈癌细胞自噬与Wnt/β-catenin信号通路关系的研究进展

自噬是真核细胞内发生的一种高度保守的自我降解机制,宫颈癌的肿瘤细胞自噬是肿瘤进展的重要因素。自噬作用的下调与宫颈细胞HPV感染、宫颈癌的产生存在紧密联系。Wnt信号通路在宫颈癌细胞的自我更新和分化的调控中扮演重要角色,越来越多的研究证明Wnt信号通路表达的激活及β-catenin的异常表达与宫颈癌密切相关。宫颈癌细胞自噬与Wnt/β-catenin信号通路之间存在一定关系并相互作用,影响着癌症的发生发展。本文就宫颈癌细胞自噬与Wnt/β-catenin信号通路关系综述如下。     

自噬在肿瘤中的双重作用

自噬是一种溶酶体降解途径, 通过对细胞内变性蛋白或受损细胞器进行降解, 以维持细胞内物质循环及代谢调节的稳定。自噬是一把双刃剑, 在肿瘤微环境中, 自噬既能在不利环境中提高肿瘤细胞对应激的耐受能力, 维持其生存, 又能在肿瘤发展的不同阶段抑制其产生和转移, 甚至成为某些凋亡缺陷肿瘤细胞的死亡途径。此外, 自噬的双重作用还表现在癌症治疗过程中。因此, 深入探讨自噬在肿瘤中的双重作用有助于为肿瘤防治提供新思路。      

细胞自噬及其在乳腺癌中的研究进展

自噬是一种在生物进化过程中发生的细胞分解代谢过程,细胞内膜结构、蛋白质复合物和溶酶体形成自噬溶酶体用于降解和更新细胞成分.自噬是为细胞内稳态以及适应压力而发生的生理性调节,自噬机制发生改变会导致不同的病理条件.在肿瘤中自噬是复杂的,并且具有双面效应.在多种乳腺癌类型中,自噬有希望成为一种新的靶向治疗策略.本文旨在总结在肿瘤转移中自噬参与调节的主要分子机制,以及在肿瘤治疗中自噬所起的作用.     

Autophagic tumor stroma: Mechanisms and roles in tumor growth and progression

Macroautophagy (hereafter autophagy) is a cellular homeostatic mechanism that involves protein and organelle degradation, and has a number of connections to human physiology and diseases. Autophagy in tumor parenchyma acts as either a tumor‐promoting role or a tumor‐inhibiting role depending on the types and stages of tumors. In recent years, attention to autophagy in tumor stroma that is referred as “autophagic tumor stroma” has created a new paradigm to understand the role of autophagy in cancer. Here we propose that the autophagic tumor stroma is a phenomenon of adaptation at a certain stage of tumor development, and has a prominent role in tumor growth, progression and spread of tumors. This idea is supported by recent studies: (i) Autophagic tumor stroma is activated by hypoxia and cancer cells induced oxidative stress, when tumors grow to a certain stage; (ii) Autophagic tumor stroma aids in providing essential nutrients to malignant cells, remodeling the tumor microenvironment, increasing DNA damage, genetic instability and stemness in cancer cells, and decreasing the apoptotic sensitivity of cancer cells. The autophagic tumor stroma is therefore a significant determinant in tumor growth and progression and implicates an important target for cancer therapies.