三氧化二砷对人肝癌细胞作用的研究

目的：应用体外培养的肝癌细胞株(SMMC-7721)观察砷剂(As2O3)的凋亡诱导作用。方法：采用MTT法检测As2O3对肝癌细胞增殖的影响，DNA电泳及流式细胞仪检测不同浓度As2O3作用不同时间对肝癌细胞的凋亡诱导作用及细胞周期的影响。结果：As2O3抑制肝癌细胞的增殖并具有剂量-时效关系；As2O3可使肝癌细胞周期改变，与浓度有关，与作用时间未见明显关系；As2O3诱导肝癌细胞发生凋亡，并与浓度、时间有关。结论：As2O3能抑制肝癌细胞增殖，改变肝癌细胞周期，诱导肝癌细胞凋亡。     

三氧化二砷对人类肝癌细胞株端粒酶活性的影响

目的观察中药砒霜的主要成分——三氧化二砷(As2O3)对人类肝癌细胞株的端粒酶活性的影响,深入探讨As2O3注射液的抗肝癌作用机制。方法采用端粒重复序列扩增法(TRAP)结合聚丙烯酰胺凝胶电泳(PAGE)银染法,检测不同浓度和作用时间的As2O3对人类肝癌细胞株SMMC-7721和QGY-7703以及对人类正常肝细胞株L-02端粒酶活性的影响。结果人类正常肝细胞株L-02端粒酶活性为阴性,人肝癌细胞株SMMC-7721和QGY-7703端粒酶活性为阳性。不同浓度的As2O3作用24小时时对肝癌细胞株端粒酶活性未见明显抑制,而浓度20μg/ml和40μg/ml的As2O3作用48小时时可完全抑制其端粒酶活性,浓度为8、10、20和40μg/ml的As2O3作用72小时时可完全抑制其端粒酶活性。结论As2O3能够显著地选择性抑制人类肝癌细胞株端粒酶活性,且这种抑制作用呈现出典型的剂量相关性和时间依赖性。这可能是As2O3抗肿瘤作用的重要机制之一;同时提示As2O3注射液可能是一种优良的和具有临床实用价值的端粒酶抑制剂。     

三氧化二砷与顺铂合用抗人肝癌细胞株QGY-7701的实验研究

目的　探讨三氧化二砷 (As2 O3)与顺铂 (PDD)联合抗人肝癌细胞株QGY 770 1作用性质及其作用机制。方法　应用MTT法、流式细胞术分析和端粒酶活性检测等实验方法。结果　As2 O3与PDD联合应用在抑制肝癌细胞的生长繁殖、诱导肝癌细胞凋亡和抑制其端粒酶活性等方面均较各自单药的作用明显增强。结论　As2 O3与PDD联合应用具有明显的协同抗肝癌作用 ,其主要机制可能在于增强了抑制端粒酶活性。     

As2O3联合Ad-pml体外抗肝癌细胞作用的实验研究

目的:探讨三氧化二砷(As2O3)联合腺病毒介导的早幼粒细胞性白血病基因(promyelocytic leukemia-adenovirus,Ad-pml)体外抗肝癌细胞作用。方法:同时设Ad-pml组、As2O3组、As2O3联合Ad-pml组以及正常细胞对照组,运用分子生物学和细胞生物学技术,观察联合应用As2O3和Ad-pml在体外治疗肝癌的效果,并进一步探讨其作用机制及特点。结果:Ad-pml与As2O3对肝癌细胞体外生长的影响:两因素析因设计分析结果表明,单用Ad-pml处理肝癌细胞,其抑制作用随Ad-pml MOI值的增加而增加(P<0.05),单独应用As2O3在浓度小于5μmol/L时,未发现有明显的肿瘤抑制作用(P>0.05);As2O3和Ad-pml联合应用具有协同抗肿瘤作用,二者之间存在着交互作用(P<0.05)。流式细胞仪检测细胞凋亡结果:用Ad-pml和As2O3共同作用肝癌细胞24小时后,早期细胞凋亡率明显增高。RT-PCR结果表明,联合治疗组p53表达最高,而Bcl-2表达最低,相反,肝癌细胞对照组p53表达最低,而Bcl-2表达最高。结论:As2O3和Ad-pml联合应用有协同抗肝癌细胞作用,其机制与增强肝癌细胞凋亡及控制凋亡相关基因的表达有关。     

三氧化二砷与顺铂合用抗人肝癌细胞株QGY-7701的实验研究

 目的　探讨三氧化二砷 (As2 O3)与顺铂 (PDD)联合抗人肝癌细胞株QGY 770 1作用性质及其作用机制。方法　应用MTT法、流式细胞术分析和端粒酶活性检测等实验方法。结果　As2 O3与PDD联合应用在抑制肝癌细胞的生长繁殖、诱导肝癌细胞凋亡和抑制其端粒酶活性等方面均较各自单药的作用明显增强。结论　As2 O3与PDD联合应用具有明显的协同抗肝癌作用 ,其主要机制可能在于增强了抑制端粒酶活性。     

三氧化二砷对人肝癌细胞作用的研究

目的 :应用体外培养的肝癌细胞株 (SMMC 772 1)观察砷剂 (As2 O3)的凋亡诱导作用。方法 :采用MTT法检测As2 O3对肝癌细胞增殖的影响 ,DNA电泳及流式细胞仪检测不同浓度As2 O3作用不同时间对肝癌细胞的凋亡诱导作用及细胞周期的影响。结果 :As2 O3抑制肝癌细胞的增殖并具有剂量 -时效关系 ;As2 O3可使肝癌细胞周期改变 ,与浓度有关 ,与作用时间未见明显关系 ;As2 O3诱导肝癌细胞发生凋亡 ,并与浓度、时间有关。结论 :As2 O3能抑制肝癌细胞增殖 ,改变肝癌细胞周期 ,诱导肝癌细胞凋亡     

三氧化二砷应用于肝癌治疗的实验研究进展

三氧化二砷（arsenic trioxide，As2O3）是中药砒霜的主要成分，有剧毒，但近年来人们研究发现其具有显著的抗肿瘤作用。综述其在肝癌治疗方面的实验研究进展，阐明As2O3的抗肿瘤机制主要为通过调控多种基因选择性诱导肝癌细胞凋亡、选择性细胞毒作用、抗肿瘤血管形成作用、改变肝癌细胞核基质蛋白成分及抑制肝癌细胞增殖细胞抗原（PCNA）的表达等；细胞周期分析显示As2O3可以阻滞肝癌细胞于S＋G2／M期；与ADM、DDP等化疗药物联合应用可明显提高对肝癌细胞的杀伤率，丁硫氨酸亚矾氨（BSO）可增加肝癌细胞对As2O3敏感性。     

三氧化二砷对人肝癌SMMC-7721细胞侵袭转移能力的影响

目的:探讨三氧化二砷(As2O3)对人肝癌SMMC-7721细胞黏附、侵袭、转移能力的影响以及其机制。方法:采用MTT法观察人肝癌SMMC-7721细胞经As2O3作用前后对基底膜黏附能力的影响;Transwell膜侵袭系统观察SMMC-7721细胞经As2O3作用前后游走与穿透基底膜能力的改变。免疫细胞化学方法检测人肝癌细胞经As2O3作用前后CD44V6表达的改变。结果:As2O3能显著抑制人肝癌SMMC-7721细胞与m arigel的黏附、抑制细胞游走与穿透基底膜的作用(P<0.05),能抑制人肝癌细胞CD44v6的表达(P<0.05)。结论:As2O3具有抑制人肝癌细胞的侵袭、转移能力,其抑制作用可能与CD44v6的表达下调有关。     

三氧化二砷对人肝癌SMMC-7721细胞侵袭转移能力的影响

目的：探讨三氧化二砷（As2O3）对人肝癌SMMC-7721细胞黏附、侵袭、转移能力的影响以及其机制。方法：采用MTT法观察人肝癌SMMC-7721细胞经As2O3作用前后对基底膜黏附能力的影响;Transwell膜侵袭系统观察SMMC-7721细胞经As2O3作用前后游走与穿透基底膜能力的改变。免疫细胞化学方法检测人肝癌细胞经As2O3作用前后CD44V6表达的改变。结果：As2O3能显著抑制人肝癌SMMC-7721细胞与m arigel的黏附、抑制细胞游走与穿透基底膜的作用（P〈0.05）,能抑制人肝癌细胞CD44v6的表达（P〈0.05）。结论：As2O3具有抑制人肝癌细胞的侵袭、转移能力,其抑制作用可能与CD44v6的表达下调有关。     

As2O3联合L-OHP对HepG2肝癌细胞株的体外抑制作用

目的探讨As2O3联合L-OHP对HepG2肝癌细胞株的体外抑制作用。方法采用MTT法（四唑盐比色法）动态观察As2O3联合L-OHP对HepG2肝癌细胞的生长抑制作用,并采用两药相互作用系数（CDI）来评价两药相互作用的性质;应用流式细胞术（FCM）检测凋亡率和细胞周期分布。结果 As2O3与L-OHP联合应用,对HepG2肝癌细胞株的生长抑制、诱导凋亡作用均较相应的单药增强。流式细胞直方图上可见明显的＂凋亡峰＂,且As2O3使肝癌细胞周期阻滞于G2/M期,L-OHP使细胞周期阻滞于S期和G2/M期,两药合用使细胞周期阻滞于S期和G2/M期。结论中低浓度As2O3与L-OHP联合作用具有显著的协同效益,其主要机制可能是As2O3联合L-OHP诱导肝癌细胞凋亡作用及增强细胞周期阻滞作用。     

Arsenic compounds in the treatment of multiple myeloma: a new role for a historical remedy

Arsenic compounds have been used since ancient times to treat a wide variety of ailments. Although the use of arsenic to treat hematologic cancers has been documented since the 19th century, widespread use of arsenic compounds in patients with hematologic malignancies did not occur until the 1990s, when several groups in China reported impressive clinical response rates in patients with acute promyelocytic leukemia who had received arsenic trioxide. Subsequently, clinical studies conducted in the United States confirmed earlier reports, and arsenic trioxide was approved by the Food and Drug Administration for the treatment of relapsed/refractory acute promyelocytic leukemia. The use of arsenic compounds in the treatment of multiple myeloma (MM) is supported by the proposed mechanisms of action underlying the antitumor activity of arsenic and by preclinical studies showing antiproliferative and cytotoxic activities in cell culture and animal models. Moreover, clinical studies of arsenic compounds, particularly arsenic trioxide-based regimens, have shown that this drug is clinically active in patients with relapsed/refractory MM. Combination studies with other antimyeloma agents have shown evidence of synergy with arsenic trioxide. Furthermore, arsenic trioxide-based regimens in MM appear to be well tolerated, particularly with regard to cardiac toxicity. The activity and tolerability observed in clinical studies promise to make arsenic-based chemotherapy a viable treatment option for patients whose disease does not respond to or who cannot tolerate other chemotherapy regimens.     

三氧化二砷作用机制研究进展

砷化合物在我国作为药物应用已有2400多年的历史了。自从20世纪90年代,我国学者应用三氧化二砷（As2O3）治疗急性早幼粒细胞性白血病并获得成功以来,人们对砷化合物进行了深入的研究,发现As2O3不仅对各型白血病有效,对其他多种恶性肿瘤也有良好的治疗效果。As2O3主要是通过抑制肿瘤细胞生长和肿瘤新生血管形成、诱导肿瘤细胞部分分化和凋亡等发挥抗肿瘤作用的。本文不仅对上述问题进行总结,还展望了新发展起来的基因表达谱分析技术--基因芯片技术在研究As2O3作用机制方面的应用前景。     

MicroRNA-dependent regulation of PTEN after arsenic trioxide treatment in bladder cancer cell line T24

Arsenic trioxide has shown remarkable biological activity against bladder cancer in some clinical studies. However, the mechanism of its action is unknown. Our aim was to find the relationship between miRNAs and arsenic trioxide treatment by using T24 human bladder carcinoma cells. By performing microRNA microarray and quantitative real-time PCR after ATO treatment, we found that expression levels of several miRNAs, in particular, miRNA-19a, were significantly decreased in T24 cell line. Furthermore, cell proliferation assay, flow cytometry analysis, prediction of miRNA targets, Western blot analysis, and luciferase reporter assay were performed to determine the role of mir-19a in affecting the biological behaviors of T24 cells. Several miRNAs were up-regulated or down-regulated in T24 cells treated with arsenic trioxide compared to their controls. If only changes above two folds were considered, two miRNAs were identified, miRNA-19a was down-regulated, while miRNA-222* was up-regulated. Among them, knockdown of miRNA-19a by anti-miRNA-19a transfection showed a positive therapeutic effect in bladder cancer cells by inhibiting cell growth and inducing cell apoptosis targeting PTEN through the PTEN/Akt pathway. Besides this, a synergy effect was detected between knockdown of miRNA-19a and arsenic trioxide. Arsenic trioxide altered miRNA expression profile in T24 cells. It seems miRNA-19a plays a critical role in the mechanism of arsenic trioxide treatment in bladder cancer. The synergy effect between miRNA-19a and arsenic trioxide that advocates targeting the mir-19a may represent a potential approach to enhance the efficacy and safety of ATO to treat bladder cancer by a decrease in dose.     

缺氧时5-Fu、As2O3联合及序贯治疗对肝癌细胞凋亡的影响

目的探讨缺氧时5-氟尿嘧啶(5-fluorouracil,5-Fu)和三氧化二砷(As2O3)联合及序贯治疗对肝癌细胞凋亡的影响。方法采用MTT法,分析2种药物联合治疗及序贯治疗对肝癌细胞BEL-7402的细胞毒作用,流式细胞仪检测细胞周期和凋亡情况。结果与单用5-Fu及序贯用药相比,联合用药毒性明显增强,与单用5-Fu相比序贯用药毒性明显增强。联合用药可增加G1期细胞,减少S期细胞,序贯用药可减少G1期细胞,增加S期细胞,且联合用药组细胞凋亡率较高。结论 As2O3、5-Fu可导致细胞凋亡,两者联合有协同作用,与序贯用药相比,联合用药细胞毒作用更强,细胞凋亡率更高,治疗效果更强,实验结果可为临床提供参考依据。     

Mechanisms of action of arsenic trioxide

Arsenic trioxide has shown substantial efficacy in treating both newly diagnosed and relapsed patients with acute promyelocytic leukemia (APL). As a single agent, it induces complete remissions, causing few adverse effects and only minimal myelosuppression. These successes have prompted investigations to elucidate the mechanisms of action underlying these clinical responses. Substantial data show that arsenic trioxide produces remissions in patients with APL at least in part through a mechanism that results in the degradation of the aberrant PML-retinoic acid receptor alpha fusion protein. Studies have also investigated concerns about the toxicity and potential carcinogenicity of long-term exposure to environmental arsenic. Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations in cellular function. These actions of arsenic may result in the induction of apoptosis, the inhibition of growth and angiogenesis, and the promotion of differentiation. Such effects have been observed in cultured cell lines and animal models, as well as clinical studies. Because arsenic affects so many cellular and physiological pathways, a wide variety of malignancies, including both hematologic cancer and solid tumors derived from several tissue types, may be susceptible to therapy with arsenic trioxide. These multiple actions of arsenic trioxide also highlight the need for additional mechanistic studies to determine which actions mediate the diverse biological effects of this agent. This information will be critical to realizing the potential for synergy between arsenic trioxide and other chemotherapeutic agents, thus providing enhanced benefit in cancer therapy.     

Arsenic trioxide inhibits proliferation and induces apoptosis in pancreatic cancer cells

Because of the poor therapeutic responsiveness of pancreatic cancer patients, new chemotherapeutic agents for pancreatic cancer would be extremely beneficial. The effects of arsenic trioxide in pancreatic cancer have not been explored. To evaluate the anti-pancreatic cancer effects of arsenic trioxide, three human pancreatic cell lines, HPAF, MiaPaCa-2 and PANC-1, were tested. Arsenic trioxide caused dose- and time dependent inhibition of pancreatic cancer cell proliferation. In parallel with inhibition of cell proliferation, arsenic trioxide induced significant morphological changes, including shrunken cytoplasm, membrane blebbing, and nuclear condensation consistent with apoptosis. Propidium iodide DNA staining showed an increase of the sub-G0/G1 cell population. The DNA fragmentation induced by arsenic trioxide in these three cell lines was confirmed by the TUNEL assay. Furthermore, Western blotting analysis indicated that caspase-3 was activated following arsenic trioxide as measured by procaspase-3 cleavage and PARP cleavage. These findings show that arsenic trioxide has potent anti-proliferative effects on human pancreatic cancer cells with induction of apoptosis in vitro.     

亚砷酸治疗淋巴瘤作用机制研究进展

  淋巴瘤治疗目前主要以联合化疗及放疗为主，对难治及晚期患者可通过造血干细胞移植进行治疗。近年来国内外学者用亚砷酸（As2O3）治疗淋巴瘤获得了一定疗效。就As2O3对淋巴瘤细胞的实验研究及临床研究的进展进行综述     

三氧化二砷抗肿瘤作用研究进展

三氧化二砷治疗急性早幼粒白血病疗效肯定 ,但对其他血液肿瘤及实体瘤的治疗作用及抗肿瘤作用机理仍末明确。综述国内、外有关研究 ,探索其治疗作用及抗肿瘤机制 ,为开辟三氧化二砷新的治疗作用提供参考。     

三氧化二砷诱导恶性肿瘤细胞凋亡机制的研究进展

三氧化二砷已广泛应用于白血病和各种实体瘤化学治疗的基础研究和临床实践中。近年来国内外多项研究证实三氧化二砷诱导凋亡是其杀伤肿瘤的主要机制,其分子机制尚未得到系统阐明,本文就其抗凋亡作用机制的研究进展作一综述。