盐霉素和盐霉素钠对人乳腺癌干细胞和乳腺癌细胞体外细胞毒作用的比较(英文)

盐霉素是一种从白色链丝菌培养物中分离提取的聚醚类离子载体型抗生素,它广泛应用于畜禽类动物鸡球虫病的防治,并且还能作为饲料添加剂以促进畜禽的生长。最近新发现盐霉素具有特异性抑制肿瘤干细胞的作用。目前盐霉素钠的价格只是盐霉素的十分之一,但两者在抑制肿瘤细胞和肿瘤干细胞方面的异同却未见文献报导。本研究以人乳腺癌细胞MCF-7及其干细胞为模型,通过SRB实验对盐霉素及其钠盐的细胞毒性进行了评价和比较。首先,通过流式细胞仪从MCF-7细胞中分选得到了SP细胞;然后用乳腺癌干细胞表面特异性标志物CD44~+/CD24~-对SP细胞进行了鉴定;最后,分别测定了盐霉素和盐霉素钠对分选得到的肿瘤干细胞和肿瘤细胞的体外生长抑制率。结果表明,与乳腺癌细胞相比较,盐霉素和盐霉素钠对肿瘤干细胞均表现出了更强的抑制作用,在同样的给药浓度下,盐霉素和盐霉素钠对肿瘤细胞和肿瘤干细胞的抑制作用未表现出明显的差异。本研究结果提示,在抑制肿瘤干细胞的相关研究中,可以用盐霉素钠替代盐霉素而不会影响抑制效果。     

盐霉素的抗癌作用研究新进展

盐霉素是从白色链霉菌发酵液中分离出的一种新型具有生物活性的物质.经研究表明,盐霉素可以抑制多种肿瘤干细胞的生长转移,增加肿瘤细胞对药物治疗的敏感性,诱导其凋亡,抵抗其耐药,能选择性地杀伤肿瘤细胞,对乳腺癌、肝癌、肺癌等均有效果.本文介绍了近年来盐霉素抗肿瘤作用的最新进展,为后续临床研发和恶性肿瘤治疗提供了新希望.     

沙利度胺合并环磷酰胺的抗肿瘤作用及相关作用机制研究

考察了沙利度胺单用及合并环磷酰胺的抗肿瘤作用.通过观察药物对人脐静脉内皮细胞HUVEC迁移、管腔形成、凋亡的影响及免疫组化、microPET成像等试验探讨沙利度胺抗肿瘤的作用机制.结果表明,沙利度胺具有一定的抑制肿瘤细胞增殖的作用,与环磷酰胺合用时效果较好.沙利度胺能诱导HUVEC和H22肿瘤细胞的凋亡,阻止HUVEC迁移和管腔形成,减少肿瘤中微血管数目.     

沙利度胺合并环磷酰胺的抗肿瘤作用及相关作用的机制研究

目的研究沙利度胺合并环磷酰胺的抗肿瘤作用及机制。方法培养XB1279人结肠癌细胞,给予沙利度胺、环磷酰胺处理后进行荧光定量PCR和MTT检测。结果沙利度胺能抑制VEGFA的表达、促进sFlt-1的表达且具有剂量效应,环磷酰胺能抑制细胞活力且具有剂量效应。结论沙利度胺能够抑制肿瘤血管生长的过程,环磷酰胺能够直接抑制肿瘤细胞的增殖过程,两种药物联合使用能发挥抗肿瘤作用。     

唑来膦酸在乳腺癌中抗肿瘤差别化效应的研究进展

乳腺癌是女性发病率和死亡率较高的恶性肿瘤。 肿瘤复发和远处转移是导致死亡的主要原因。 唑来膦酸（ZOL）具有潜在抑制破骨细胞介导的骨吸收的特性, 既可抑制肿瘤细胞增殖和启动肿瘤细胞凋亡, 又可干扰肿瘤细胞与骨基质的黏附, 从而抑制肿瘤细胞的迁移和侵袭。 一些临床前研究已经证实 ZOL 具有直接抗肿瘤作用, 且在对绝经前和绝经后乳腺癌患者的治疗效果上有差异。 本文就 ZOL 在乳腺癌中抗肿瘤差别化效应的基础及临床研究进展作一综述。     

盐霉素针对肿瘤干细胞的治疗机制

肿瘤干细胞是存在于肿瘤组织中的一小部分具有干细胞性质的细胞群体,它具有自我更新的能力,是形成不同分化程度肿瘤细胞和肿瘤不断扩大的源泉。而现有的治疗肿瘤的方法多是针对一般肿瘤细胞,而非肿瘤干细胞,治疗不彻底,仍会造成肿瘤的复发和转移。因此,开发新的药物杀灭肿瘤干细胞是现今治疗肿瘤的重点。盐霉素由于具有逆转多药耐药、抑制凋亡、调整细胞周期、抑制DNA修复等特点,可应用于肿瘤干细胞的治疗。     

植物甾醇的抗肿瘤作用及其机制研究进展

植物甾醇是植物中的一种活性成分,近年来国外对其抗肿瘤作用及其机制研究颇多。植物甾醇对结肠癌、乳腺癌和前列腺癌都有预防和治疗作用。其作用机制主要为抑制癌症物质产生,抑制肿瘤细胞生长和繁殖;还可以改变肿瘤细胞的信号传导,抑制肿瘤细胞转移,刺激产生肿瘤免疫应答。     

塞来昔布抗肿瘤效应及其作用机制的研究进展

塞来昔布是一种特异性环氧化酶-2抑制剂,具有抗炎、镇痛和退热作用。近年来,塞来昔布的抗肿瘤作用受到广泛关注,已被应用于消化道肿瘤、乳腺癌、肺癌、肝癌、前列腺癌等的化学辅助治疗和放射治疗增敏。综述了塞来昔布的抗肿瘤效应,并总结了其作用机制,如抑制肿瘤细胞增殖、抑制肿瘤细胞侵袭和转移、抑制肿瘤新生血管生成、诱导肿瘤细胞分化、诱导肿瘤细胞凋亡、调节肿瘤免疫、逆转肿瘤细胞的多药耐药性,以期为塞来昔布的深入研究和临床肿瘤防治提供用药参考。     

人参皂苷Rg3的抗肿瘤作用及其机制研究

人参皂苷Rg3作为传统中药人参的有效成分之一,具有明显的抗肿瘤作用,也是我国自行研制的第一个应用于临床的抗肿瘤转移复发的一类中药新药参一胶囊的主要活性成分。本文从人参皂苷Rg3对胃癌、肺癌、肠癌、乳腺癌、肝癌等不同肿瘤的作用,以及其诱导肿瘤细胞凋亡、抑制肿瘤细胞增殖、侵袭和转移、抑制肿瘤血管生成、逆转肿瘤耐药作用、影响肿瘤信号传导相关基因的表达、增强患者免疫能力等方面,对其抗肿瘤作用及机制的研究进展进行了综述。     

手霉素抗肿瘤及诱导细胞凋亡作用的实验研究

目的 研究手霉素(manumycin)的体外抗肿瘤及其诱导肿瘤细胞凋亡的作用,初步探讨手霉素抗肿瘤作用机制,为将来这种新型药物的抗肿瘤作用开发提供理论基础和临床应用提供试验依据.方法 MTT法检测药效动力学特征;采用Gimsa染色技术、透射电镜技术、流式细胞技术、DNA提取及琼脂糖凝胶电泳技术测定和观察癌细胞凋亡的情况;流式细胞技术检测凋亡相关基因bcl-2、bax表达水平.结果 手霉素抑制细胞生长呈时效和量效关系;Gimsa染色、透射电镜结果 显示手霉素诱导人乳腺癌细胞株MCF-7出现较典型的细胞凋亡形态学变化及超微结构改变;流式细胞分析的DNA直方图上可见G1期峰出现细胞凋亡峰亚G1期峰,乳腺癌细胞的周期也发生了改变,多数细胞被阻滞在G2/M期;琼脂糖凝胶电泳可观察到具有凋亡特征的梯形条带;流式细胞仪分析的实验结果 显示手霉素作用MCF-7细胞前后bcl-2和bax蛋白表达水平无明显改变.结论 (1)手霉素体外具有很强的抗肿瘤作用,可以抑制多种细胞增殖.(2)诱导肿瘤细胞凋亡是手霉素发挥抗肿瘤作用的一条重要途径.经手霉素作用后,肿瘤细胞bcl-2和bax蛋白表达水平无明显变化,手霉素诱导肿瘤细胞凋亡作用并非通过调控bcl-2和bax的表达水平实现.     

Salinomycin overcomes acquired tamoxifen resistance through AIB1 and inhibits cancer cell invasion in endocrine resistant breast cancer

Salinomycin is a monocarboxylic polyether ionophore isolated from Streptomyces albus. It has been widely used as an antibiotic in veterinary medicine in poultry. A recent study demonstrated that salinomycin selectively inhibits human breast cancer stem cells; one possible mechanism of tamoxifen resistance. Our results show that salinomycin is effective in inhibiting MCF‐7/LCC2 and MCF‐7/LCC9 cell lines which are well‐established endocrine resistant cells and has a synergistic effect in combination with tamoxifen using MTT proliferation assay. The inhibitory effect of salinomycin on the reduction of critical ER co‐activator; amplified breast 1 (AIB1) mRNA and protein expression is overcoming tamoxifen resistance . Moreover, salinomycin significantly inhibits cell invasion in Matrigel invasion assay. The effect was mediated at least in part by the decrease of matrix metalopeptidase 9 (MMP‐9) which is one critical enzyme facilitated in the cell invasion process. In conclusion, salinomycin should be developed as a novel agent used alone or in combination for endocrine‐resistant breast cancer.     

Salinomycin: a new cancer drug candidate

Very recently, it has been shown that it is possible to selectively kill breast cancer stem cells using the ionophore antibiotic, salinomycin. Its ability to kill cancer stem cells and apoptosis-resistant cancer cells may define salinomycin as a novel anticancer drug.     

盐霉素纳米制剂的研究进展

盐霉素（salinomycin,SAL）作为一种抗生素,已广泛用于畜牧业,近年来研究人员发现该药对多种肿瘤及肿瘤干细胞具有较强的抑制作用,而且体内外研究及早期临床试验结果均表明SAL具有抗肿瘤多重耐药活性,有望成为一种新型的抗肿瘤药物。但是,SAL的水溶性较差,且有一定的毒副作用,为获得更好的治疗效果,SAL制剂学的研究得到药学界的广泛关注。本文对近年来SAL纳米制剂的研究进展进行综述。     

盐霉素对乳腺癌 MCF-7 球囊细胞增殖与上皮间质转化作用的研究

摘要：目的 探讨盐霉素（Salinomycin）对MCF-7球囊细胞（MCF-7 MS）的增殖与上皮间充质转化 (EMT）的作用。方法 通过乳腺癌MCF-7细胞无血清悬浮培养富集乳腺癌干细胞（BCSCs）得到MCF-7 MS;CCK-8 assay检测0、10、30、100、300、1 000、3 000及10 000 nmol/L的浓度盐霉素处理24 h对MCF-7 MS细胞生存率的影响,并计算半抑制浓度（IC50）值。 Western blot检测30 nmol/L、60 nmol/L终浓度的盐霉素对MCF-7 MS细胞上皮标志物E-钙黏蛋白(E-cadherin)和间质化标志物Snail的表达影响,以等体积的DMSO处理的MCF-7 MS细胞作为对照组。BALB/c裸鼠皮下接种MCF-7 MS细胞制备荷瘤鼠模型并分为对照组（等体积的生理盐水）和盐霉素给药组（5 mg/kg盐霉素）,免疫组织化学染色检测瘤组织的Snail和E-cadherin的表达。结果 随着浓度的增加,MCF-7 MS细胞的存活率逐渐下降（P < 0.05）,24 h的IC50值为989 n mol/L。与对照组比较,30和60 nmol/L的盐霉素均可增加E-cadherin的表达,而降低Snail的表达,且后者作用更明显（P < 0.05）。与对照组相比,盐霉素给药组荷瘤鼠瘤组织内的Snail的表达下调,而E-cadherin的表达升高（P < 0.01）。结论 盐霉素能够抑制具有BCSCs特性的MCF-7 MS细胞的增殖,且可抑制MCF-7 MS细胞的EMT,是靶向肿瘤干细胞潜在药物。     

Triggering of Erythrocyte Cell Membrane Scrambling by Salinomycin

Salinomycin, a polyether ionophore antibiotic effective against a variety of pathogens, has been shown to trigger apoptosis of cancer cells and cancer stem cells. The substance is thus considered for the treatment of malignancy. Salinomycin compromises tumour cell survival at least in part by interference with mitochondrial function. Erythrocytes lack mitochondria but may undergo apoptosis‐like suicidal cell death or eryptosis, which is characterized by scrambling of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Signalling involved in the triggering of eryptosis includes activation of oxidant‐sensitive Ca²⁺ permeable cation channels with subsequent increase in cytosolic Ca²⁺ activity ([Ca²⁺]_i). This study explored whether salinomycin stimulates eryptosis. Phosphatidylserine‐exposing erythrocytes were identified by measurement of annexin‐V binding, cell volume was estimated from forward scatter, haemolysis determined from haemoglobin release, [Ca²⁺]_i quantified utilizing Fluo3‐fluorescence and oxidative stress from 2′,7′ dichlorodihydrofluorescein diacetate (DCFDA) fluorescence in flow cytometry. A 48‐hr exposure to salinomycin (5‐100 nM) was followed by a significant increase in Fluo3‐fluorescence, DCFDA fluorescence and annexin‐V binding, as well as a significant decrease in forward scatter (at 5–10 nM, but not at 50 and 100 nM). The annexin‐V binding after salinomycin treatment was significantly blunted but not abrogated in the nominal absence of extracellular Ca²⁺ or in the presence of antioxidant n‐acetyl cysteine (1 mM). Salinomycin triggers cell membrane scrambling, an effect at least partially due to oxidative stress and entry of extracellular Ca²⁺.     

Salinomycin induces apoptosis in cisplatin-resistant colorectal cancer cells by accumulation of reactive oxygen species

Postoperative chemotherapy for Colorectal cancer (CRC) patients is not all effective and the main reason might lie in cancer stem cells (CSCs). Emerging studies showed that CSCs overexpress some drug-resistance related proteins, which efficiently transport the chemotherapeutics out of cancer cells. Salinomycin, which considered as a novel and an effective anticancer drug, is found to have the ability to kill both CSCs and therapy-resistant cancer cells. To explore the potential mechanisms that salinomycin could specifically target on therapy-resistant cancer cells in colorectal cancers, we firstly obtained cisplatin-resistant (Cisp-resistant) SW620 cells by repeated exposure to 5 μmol/l of cisplatin from an original colorectal cancer cell line. These Cisp-resistant SW620 cells, which maintained a relative quiescent state (G0/G1 arrest) and displayed stem-like signatures (up-regulations of Sox2, Oct4, Nanog, Klf4, Hes1, CD24, CD26, CD44, CD133, CD166, Lgr5, ALDH1A1 and ALDH1A3 mRNA expressions) (p < 0.05), were sensitive to salinomycin (p < 0.05). Salinomycin did not show the influence on the cell cycle of Cisp-resistant SW620 cells (p > 0.05), but could induce cell death process (p < 0.05), with increased levels of LDH release and MDA contents as well as down-regulations of SOD and GSH-PX activities (p < 0.05). Our data also showed that the pro-apoptotic genes (Caspase-3, Caspase-8, Caspase-9 and Bax) were up-regulated and the anti-apoptotic gene Bcl-2 were down-regulated in Cisp-resistant SW620 cells (p < 0.05). Accumulated reactive oxygen species and dysregulation of some apoptosis-related genes might ultimately lead to apoptosis in Cisp-resistant SW620 cells. These findings will provide new clues for novel and selective chemotherapy on cisplatin-resistant colorectal cancer cells.     

Comparative determination of salinomycin by high-performance liquid chromatography, microbiological and colorimetric methods in testing production processes and animal feed preparations

Salinomycin and other polyether antibiotics usually do not have a strong chromophore, nor electrochemical or fluorescence activity. Consequently, common liquid chromatography detectors cannot be used for the direct determination of these substances and LC methods that utilize a specific post-column reaction with vanillin have been developed to overcome this limitation. In this report, some modifications of previously published LC methods were made to optimize the analysis of salinomycin. Comparison with standard microbiological and colorimetric methods has been carried out. The LC method was found to provide the best way of precise, and accurate determination in low levels of salinomycin down to the concentration of 1 mg kg-1.     

Comparative determination of salinomycin by high-performance liquid chromatography, microbiological and calorimetric methods in testing production processes and animal feed preparations

Salinomycin and other polyether antibiotics usually do not have a strong chromophore, nor electrochemical or fluorescence activity. Consequently, common liquid chromatography detectors cannot be used for the direct determination of these substances and LC methods that utilize a specific post-column reaction with vanillin have been developed to overcome this limitation. In this report, some modifications of perviously published LC methods were made to optimize the analysis of salinomycin. Comparison with standard microbiological and colorimetric methods has been carried out. The LC method was found to provide the best way of precise, and accurate determination in low levels of salinomycin down to the concentration of 1 mg kg⁻¹.     

Reversing breast cancer stem cell into breast somatic stem cell

Stem cells have an important role in cell biology, allowing tissues to be renewed by freshly created cells throughout their lifetime. The specific micro-environment of stem cells is called stem cell niche; this environment influences the development of stem cells from quiescence through stages of differentiation. Recent advance researches have improved the understanding of the cellular and molecular components of the micro-environment--or niche--that regulates stem cells. We point out an important trend to the study of niche activity in breast cancers. Breast cancer has long been known to conserve a heterogeneous population of cells. While the majority of cells that make up tumors are destined to differentiate and eventually stop dividing, only minority populations of cells, termed cancer stem cell, possess extensive self renewal capability. These cancer stem cells possess characteristics of both stem cells and cancer cells. Breast cancer stem cells reversal to breast somatic stem cells offer a new therapy, that not only can stop the spread of breast cancer cells, but also can differentiate breast cancer stem cells into normal breast somatic stem cells. These can replace damaged breast tissue. Nevertheless, the complexity of realizing this therapy approach needs further research.