Induction of apoptosis by arsenic trioxide and hydroxycamptothecin in gastric cancer cells in vitro

AIM To study the effects of arsenic trioxide andHCPT on different degrees of differentiated gastriccancer cells（SGC-7901,MKN-45,MKN-28）withrespect to both cytotoxicity and induction ofapoptosis in vitro.METHODS The cytotoxicity of As2O3 and HCPTon gastric cancer cells was determined by MTTassay.Morphologic changes of apoptosis ofgastric cancer cells were observed by lightmicroscopy and transmission electron microscopy.Apoptosis and cell cycle changes of gastric cancercells induced by HCPT and As2O3 were investigatedby TUNEL method and flow cytometry.RESULTS As2O3 and HCPT had remarkablecytotoxic effects on different degrees ofdifferentiated gastric cancer cells.The IC50ofAs2O3 on well differentiated gastric cancer cellMKN-28,moderately differentiated gastric cancercell SGC-7901,and poorly differentiated gastriccancer cell MKN-28 were 8.91 μmol/L,10.57μmol/L,and 11.65 μmol/L,respectively.The IC50of HCPT on MKN-28,SGC-7901,and MKN-45 were9.35 mg/L,10.21 mg/L,and 12.63 mg/Lrespectively after 48 h treatment.After 12 h ofexposure to both drugs,gastric cancer cellsexhibited morphologic features of apoptosis,including cell shrinkage,nuclear condensation, and formation of apoptotic bodies.A typicalsubdiploid peak before G0/G1 phase was observedby flow cytometry.The apoptotic rates of SGC-7901,MKN-45,and MKN-28 were 13.84%,22.52%,and 9.68%,respectively after 48 hexposure to 10 μmol/L As2O3.The apoptotic ratesof SGC-7901,MKN-45,and MKN-28 were 21.88%,12.35%,and 30.26%,respectively after 48 hexposure to 10 mg/L HCPT.The apoptotic indicewere 7%-15% as assessed by TUNEL method.The effect of As2O3 on SGC-7901 showedremarkable cell cycle specificity,which inducedcell death in G1 phase,and blocked G2/M phase.HCPT also showed a remarkable cell cyclespecificity,by inducing cell death and apoptosis inG1 phase and arrest of proliferation at S phase.CONCLUSION As2O3 and HCPT exhibitsignificant cytotoxicity on gastric cancer cells byinduction of apoptosis.As2O3 and HCPT mighthave a promising prospect in the treatment ofgastric cancer,which needs to be further studied.

A study on arsenic trioxide inducing in vitro apoptosis of gastric cancer cell lines

INTRODUCTION Cell apoptosis,which involves the biologic regulation of the numbers and vital activity of cells,is an important metaboloc process in both normal cells and tumor cells.

Cell cycle arrest and apoptotic cell death in cultured human gastric carcinoma cells mediated by arsenic trioxide

AIM: To investigate the effect of arsenic trioxide on human gastric cancer cell line MKN45 with respect to both cytotoxicity and induction of apoptosis in vitro. METHODS: MKN45 cells were treated with arsenic trioxide(As2O3) at the concentration of 1, 5, and 10 μmol/L,respectively, for three successive days. Cell growth and proliferation were observed by cell counting and trypanblue exclusion. Cytotoxicity of As2O3 was determined by MTT assay. Morphologic changes were studied with light microscopy. Flow cytometry was used to assay cell DNA distribution and apoptotic cells were confirmed with terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL) and DNA electrophoresis.RESULTS: The growth of MKN45 cells was significantlyinhibited by As2O3 which was confirmed by colony-forming assay. After 7 d of culture with various concentrations of As2O3, colony-forming capacity of MKN45 cells decreased with As2O3 increment in comparison with that of control group. The inhibitory rate of colony-formation was 38.5%, 99.1%, and 99.5% when the concentration of As2O3 was1, 5, and 10 iμmol/L in culture medium, respectively. The cell number of a single colony in drug treatment groups was less than that of control group. The cell-killing rate of As2O3 to MKN45 cells was both dose- and timedependent with an IC50 of (11.05±0.25) μmol/L. After incubation in 10 μmol/L As2O3 for 24 h, the cell-killing rate was 27.1%, and it was close to 50% after 48 h. The results showed that As2O3 induced time- and dosedependent apoptosis in MKN45 cells, blocked at G2/M phase. The apoptotic peak (sub-G1 phase) appeared and cell apoptotic rate in MKN45 cells was 18.3-32.5% aftertreatment by 10 μmol/L As2O3 for 48 h. The percentage of G2/M cell of the experimental groups was 2.0-5.0 times than that of the control group. Gel electrophoresis of DNA from cells treated with each concentration of As2O3 for 48 h revealed a 'ladder' pattern, indicating preferential DNA degradation at the internucleosomal, linker DNA sections. TUNEL also demonstrated strand breaks in DNA of MKN45 cells treated with As2O3, while control cellsshowed negative labeling.CONCLUSION: As2O3 can induce apoptosis of human gastric carcinoma cells MKN45, which is the basis of its effectiveness. It shows great potential in the treatment of gastric carcinoma.

Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods: The microculture tetrazoli-um (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cy-tometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse tran-scription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53 and c-myc. Results: As2O3 inhibited the growth of RCC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells, but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion: As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

STUDY ON EFFECTS OF ARSENIC TRIOXIDE ON GASTRIC CANCER CELL LINES

Objective To evaluate the effects of arsenic trioxide (As-2O-3) on apoptosis and differentiation of gastric cancer cell lines (GCCL). Methods MKN45 and SGC7901 cells were treated with As-2O-3 at different concentrations, then the apoptosis rates and cell cycle were determined by flow cytometry assays, the morphologic changes were observed under fluorescence microscopy and electronic microscopy, and the gene expressions were tested with immunohistologic staining. Results Higher apoptosis rates of GCCL were seen in the As-2O-3-treated group at concentrations of 5μmol and 10μmol, as compared with those in the 5-Fu-treated group. Cell-nuclear pyknosis and chromosomal condensation were observed. The As-2O-3 at a concentration of 0.5 μmol could induce the cell cycle changes of GCCL, revealing an increase in the proportion of G1/G0 phase cells and a decrease in the proportion of S phase cells. From the fifth day after treatment of SGC7901 with As-2O-3 at a low concentration, P53 and bcl-XL genes expression rates were reduced, Bax gene expression rate increased, and bcl-2 gene expression showed little change. Conclusion As-2O-3 could induce GCCL apoptosis at a high concentration and differentiation at a low concentration, but it could not completely reverse the malignant biological behaviours of cancer cells.

Impact of Arsenic Trioxide on LS-174T Cell Growth in vitro and the Activity of Telomerase

The therapeutic action of arsenic trioxide（ As203 ） on solid tumors has aroused widespread interest among scholars. To study the impact of As2O3 on human colorectal carcinoma cells（ LS-174T cell） and the activity of telomerase, the methods of PCR-ELISA, flow cytometry （FCM） and MTT assay in vitro were utilized. The results show that （1） with an increase in the concentration of As2O3, the ratio of living the cells to dead cells decreases significantly, and the IC50 value is 5.23 μg/mL; （2） the cells of the experimental groups can endure a series of morphological changes similar to the features of apoptosis ; （3） the apoptotic curves of FCM pictures appear after 24 h, and the cells show the apoptosis in a time-dependent manner; （4） As2O3 can inhibit the activity of telomerase of the cell extraction obviously in a concentration-dependent and time-dependent manner after 24 h. It can be concluded from the experiment results in vitro that As2O3 can induce the apoptosis of LS-174T cells and inhibit the telomerase activity. Therefore, it has been proposed, for the first time, that these two factors （the apoptosis of LS-174T cells and the inhibition to the telomerase activity） are important causes of the LS-174T cell death caused by As2O3.

Comparison of differential gene expression profiles in human esophageal squamous carcinoma EC8712 cells before and after arsenic trioxide (As_2O_3) treatment

To elucidate molecular mechanisms of As2O3 induced apoptosis of cancer cells in vitro, Atlas human cDNA expression analysis has been used for the profile of the known genes expressed in the human esophageal squamous carcinoma cells before and after treated by As2O3. On treating EC8712 cells with As2O3, most of the oncogenes have been down-regulated, while some tumor suppressor genes, such as DCC, up-regulated. Cyclin H decreases,

三氧化二砷诱导胃癌细胞凋亡及对相关基因表达的影响

目的 研究三氧化二砷 (As2 O3)诱导胃癌细胞的凋亡作用及对凋亡相关基因p5 3、c myc、bcl 2、bcl xl和bcl xs表达的影响 ,探讨其诱导胃癌凋亡的作用机制。方法 研究As2 O3 对胃癌细胞SGC 790 1和MKN 45的诱导凋亡作用和对凋亡相关基因表达的影响。结果 As2 O3 作用于细胞可见典型的细胞凋亡。出现典型的亚二倍体“凋亡峰”。 10 μmol/LAs2 O3 的诱导胃癌细胞SGC 790 1和MKN 45的凋亡率为13 8%和 2 2 5 %。细胞凋亡指数在 1 42 %～ 9 5 %之间。As2 O3 作用后能明显下调SGC 790 1细胞的bcl 2蛋白和mRNA的表达 ;对SGC 790 1细胞的p5 3、c myc、bcl xl和bcl xs蛋白的表达无影响。As2 O3 能促进MKN 45细胞的p5 3蛋白和mRNA的表达 ,对MKN 45细胞的bcl 2、c myc、bcl xl和bcl xs基因表达无影响。结论 As2 O3 可能通过不同途径诱导胃癌细胞凋亡 ,通过下调SGC 790 1细胞的bcl 2的蛋白表达诱导其凋亡 ,通过上调p5 3表达诱导胃癌MKN 45细胞凋亡。

As_2O_3对胃癌细胞周期及端粒酶活性的影响

目的 探讨三氧化二砷 (As2 O3 )对SGC 790 1胃癌细胞端粒酶活性及细胞周期的影响及其机制。方法 细胞凋亡、细胞周期分布及相关蛋白的表达采用流式细胞术 ;端粒酶活性的检测采用端粒末端重复序列扩增 ELISA法 (TRAP ELISA) ,端粒酶亚单位mRNA及c mycmRNA的表达采用RT PCR技术。结果 As2 O3 可明显抑制SGC 790 1细胞的生长 ,细胞凋亡率明显增加 ,G0 /G1期细胞减少 ,S和G2 /M期细胞增加 ,Bcl 2、c myc、PCNA蛋白表达减少 ,Bax蛋白表达增加 ,端粒酶活性明显下降 ;端粒酶亚单位hTR和TP1mRNA无明显变化 ,hTRTmRNA表达减少 ,同时 ,c mycmRNA的表达亦减少。结论 As2 O3 对SGC 790 1细胞的抑制作用可能是通过二条途径实现 :一个是诱导细胞凋亡 ,另一个是通过下调hTRTmRNA的表达来下调端粒酶活性 ,其机制有可能与c myc和Bcl 2基因的减少以及Bax基因的增加有关。

索拉菲尼联合三氧化二砷对肝癌细胞株的抑制作用

目的检测索拉非尼单药、As2O3单药以及两药联合对肝癌细胞株HepG2的作用,探讨两药联用的协同抗肿瘤机制。方法以不同浓度的索拉非尼和不同浓度的As2O3分别组成单药组和索拉非尼+As2O3联合用药组,另设不加药的对照组,作用于HepG2细胞。MTT法检测索拉非尼、As2O3单药及联用对HepG2细胞的增殖抑制作用,Annexin V-FITC/PI双染检测肿瘤细胞凋亡,罗丹明123染色观察细胞线粒体膜电位。Western blotting检测ERK、p-ERK蛋白表达。结果索拉非尼、As2O3单药与联用均能抑制HepG2细胞增殖,呈剂量-时间依赖效应,两药联用有交互效应(P<0.05)。索拉非尼、As2O3单药与联用均能诱导HepG2细胞凋亡,联合组更为明显(P<0.05)。两药联用能使线粒体膜电位明显下降,较两药单用和对照组有统计学意义。用药后ERK蛋白表达无明显改变,而pERK表达下降,联合用药组尤显。结论索拉非尼、As2O3单药及联用均能抑制HepG2细胞增殖,诱导其凋亡。索拉非尼与As2O3联合作用于人肝癌HepG2细胞具有协同作用,其机制可能是共同诱导线粒体膜电位下降及抑制Raf/MEK/ERK信号传导通路。

不同剂量三氧化二砷对食管癌细胞的作用

目的 :研究不同浓度As2 O3对食管癌细胞系的作用。方法 :食管恶性转化上皮细胞 (SHEEC1)是我室用人乳头状瘤病毒 (HPV) 18和TPA诱发的细胞系 ,培养在培养瓶和 2 4孔板 ,用浓度 1,3和 5 μmol/L的As2 O3处理 2 ,4 ,8,16,2 4h ,电镜检查细胞形态 ,光镜检查核分裂指数 (MI) ;用放射自显影检查 [3H] TdR掺入细胞 ;流式细胞仪检查增殖指数 (PI)和凋亡指数 (AI)。结果 :低剂量As2 O3( 1.0 μmol/L)组 [3H] TdR掺入细胞 ,MI,PI皆增加 ,提示SHEEC1增殖率提高 ;高剂量组 ( 3和 5 μmol/L)高AI和低PI,给药 2 4h后 ,电镜可见细胞凋亡和坏死。结论 :不同剂量氧化砷的作用不同 ,低剂量可引起食管癌细胞DNA合成增加和促进细胞增殖 ,高剂量则引起细胞凋亡和坏死。

三氧化二砷对肝癌细胞系BEL-7402的影响

目的 观察不同浓度的三氧化二砷作用不同时间对肝癌细胞BEL 740 2的影响及其作用机理。方法 应用不同浓度的三氧化二砷作用于肝癌细胞后 ,观察肝癌细胞的存活、形态学改变 ,并通过流式细胞仪和DNA梯状电泳观察细胞凋亡的情况。结果 不同浓度的三氧化二砷作用于肝癌细胞有明显的时间和剂量依赖性 ,发生作用后细胞生长明显受抑制 ;有明显的凋亡特征性改变 :细胞膜完整、染色质固缩、核碎裂、凋亡小体形成 ;流式细胞仪分析显示 ,肝癌细胞存在G2 /M期阻滞 ,在G1峰前出现明显的凋亡峰 ;琼脂糖凝胶电泳出现明显的凋亡特征性梯状条带。结论 三氧化二砷可明显抑制肝癌细胞的生长 ,其机理主要是诱导肝癌细胞凋亡。

三氧化二砷对胃癌细胞SGC7901多药耐药的逆转作用及其机制

研究三氧化二砷(arsenic trioxide,As2O3)对胃癌细胞多药耐药的逆转作用及其机制。逐渐递增长春新碱(VCR)的浓度诱导胃癌细胞株SGC7901产生多药耐药性(SGC7901/VCR)。MTT法测定药物对肿瘤细胞的杀伤作用;Western blotting检测肿瘤细胞内P-糖蛋白(P-gp)、谷胱甘肽S-转移酶(GST-s)表达。结果表明,胃癌SGC7901/VCR细胞对长春新碱(VCR)、5-氟尿嘧啶(5-Fu)及表阿霉素的耐药倍数分别为16.56倍、2.69倍及13.05倍。经As2O3预处理24 h后,长春新碱、5-氟尿嘧啶及表阿霉素对SGC7901/VCR的耐药倍数显著下降(P<0.05)。SGC7901/VCR在静息时细胞内P-gp、GST-s蛋白表达显著高于SGC7901。而As2O3可使SGC7901/VCR细胞内P-gp、GST-s蛋白表达显著下降,但是对SGC7901无明显作用。从而证实As2O3部分逆转SGC7901/VCR的耐药性,其机制可能与P-gp、GST-s蛋白表达降低有关。

三氧化二砷体外诱导人胃癌SGC-7901细胞凋亡的研究

目的 :探讨三氧化二砷 (As2 O3 )对人胃癌SGC 790 1细胞抑制生长、诱导凋亡的生物学效应。方法 :光学显微镜观察细胞形态 ,四甲基偶氮唑蓝 (MTT)还原法检测As2 O3 对该细胞株生长的影响 ,流式细胞仪 (FCM )及 3′ OH末端标记法(TUNEL)检测凋亡细胞。结果 :SGC 790 1细胞经As2 O3 作用后 ,细胞增殖受到明显抑制 ,且呈剂量和作用时间依赖关系 ,细胞周期分析显示G2 M期阻滞 ;FCM检测在细胞周期G1期前出现低于 2倍体的凋亡峰 ;TUNEL标记发现DNA链的断裂。结论 :As2 O3 能抑制人胃癌SGC 790 1细胞增殖 ,并诱导该细胞系凋亡 ,其发生机制可能与细胞周期阻滞有关。

As_2O_3诱导MGC803细胞凋亡中TRF1、TRF2蛋白表达及端粒稳定性的作用

目的分析三氧化二砷(As2O3)对人胃癌MGC803细胞端粒重复序列结合因子1、2(TRF1、TRF2)表达及端粒稳定性的影响,探讨As2O3诱导细胞凋亡的机制。方法体外培养MGC803细胞,MTT比色实验分析As2O3对MGC803细胞增殖抑制作用,流式细胞术检测MGC803细胞凋亡,进行染色体端-端融合分析及Westernblot检测TRF1、TRF2蛋白表达。结果MTT法显示As2O3对人胃癌MGC803细胞有明显的抑制作用,且呈时间、剂量依赖关系。流式细胞术检测出现典型的凋亡峰,并随As2O3浓度增加和作用时间延长而增高,对照组未见此改变。染色体端-端融合分析显示5μmol·L-1As2O3处理MGC803细胞48h染色体融和率明显高于对照组。Westernblot分析结果表明TRF1在5μmol·L-1As2O3处理MGC803细胞48h后,表达上升,而TRF2表达下降。结论实验结果提示As2O3通过下调TRF2蛋白表达、上调TRF1蛋白表达及使染色体端-端融合,从而诱导MGC803细胞凋亡。

三氧化二砷诱导鼻咽癌CNE1细胞凋亡及其作用机制的实验研究

目的研究三氧化二砷(As2O3)诱导人鼻咽癌细胞株凋亡作用及其相关机制。方法采用流式细胞术、电镜、TUNEL方法检测As2O3诱导CNE1细胞凋亡作用,免疫组织化学法检测As2O3对CNE1细胞p53、bcl-2和bax蛋白表达的影响。结果经As2O3处理的CNE1细胞发生凋亡,表现为FCM可检测到“亚二倍体峰”,形态学上可见核固缩,染色质边集,凋亡小体形成等改变;TUNEL法可检测到细胞内呈棕色颗粒的凋亡细胞,随着药物浓度升高,凋亡细胞发生率逐渐增多,As2O3目浓度为0.5mg/L、1.0mg/L和2.0mg/L作用48h后,CNE1细胞的凋亡指数分别为2.66±0.64、8.15±0.96和11.59±0.68,显著高于非药物处理组(0.43±0.43,P<0.05)。经As2O3处理的CNE1细胞内p53和bax蛋白表达较对照组明显增加,与凋亡指数呈正相关关系(r=0.554,P=0.011;r=0.891,P=0.000…);p53和bax蛋白表达也呈正相关关系(r=0.626,P=0.003)。结论As2O3在体外可诱导鼻咽癌CNE1细胞凋亡,其机制可能与上调p53、bax基因表达有关。

三氧化二砷对肾癌GRC-1细胞凋亡及p53、Survivin基因表达的影响

目的观察三氧化二砷(As_2O_3)对人肾癌GRC-1细胞凋亡及p53、Survivin基因表达的影响,探讨其作用机制。方法将体外培养的人肾癌GRC-1细胞分为对照组(N)和实验组,实验组根据加入As_2O_3浓度的不同分为A、B、C、D、E(2、4、6、8、10μmol/L)组。48h后,四甲基偶氮唑蓝(MTT)法测定细胞增殖,流式细胞仪检测细胞凋亡和细胞周期变化．免疫细胞化学和RT-PCR方法测定p53和Survivin基因表达。结果As_2O_3可抑制GRC-1细胞的增殖．当As_2O_3由2μmol/L增加到10μmol/L时,细胞增殖率由88．3%降低到18．7%(F= 7546．587,P＜0．01)。各实验组p53、Survivin基因表达均较对照组减少,且随着As_2O_3的增加表达呈递减改变(F=1120．741、F=6 296．535,P＜0．01)。结论As_2O_3能够抑制GRC-1细胞增殖,并且具有浓度依赖性。能将细胞阻滞在G_2/M期,诱导细胞凋亡,其作用机制与p53和Survivin基因表达水平下降有关。

生存素基因在三氧化二砷诱导腺样囊性癌-2细胞凋亡中的作用

目的体外观察三氧化二砷(As2O3)诱导人类腺样囊性癌(ACC)-2细胞凋亡的作用,同时检测此过程中ACC-2内生存素(Survivin)表达水平的变化。方法甲基噻唑基四唑(MTT)法检测As2O3不同处理条件下对ACC-2细胞生长的抑制效应,流式细胞术观察As2O3诱导的各组ACC-2细胞的凋亡率。使用逆转录聚合酶链反应(RT-PCR)检测Survivin mRNA的表达,蛋白印迹(Western blot)检测蛋白水平的表达差异。结果 As2O3作用下ACC-2细胞生长明显受抑制,其抑制率呈浓度和时间依赖关系,细胞凋亡率也呈相同的趋势。RT-PCR和Western blot检测显示,As2O3作用下ACC-2细胞内Survivin mRNA和蛋白表达明显受抑制,抑制程度也具有时间和剂量依赖性。结论 As2O3可通过促进细胞凋亡使体外培养的ACC-2细胞生长受抑制,受抑制的ACC-2细胞内Survivin mRNA和蛋白表达下降。推测Survivin基因在As2O3诱导的ACC-2细胞凋亡中起重要作用。

三氧化二砷诱导胃癌细胞AGS的凋亡及对STAT3、VEGF表达的影响

目的:探讨三氧化二砷(arsenic trioxide,As2O3)诱导胃癌细胞AGS的凋亡及对信号转导子与转录激活子基因(signal transducers and activators of transcription 3,STAT3)和血管内皮生长因子基因(vascular endothelial growth factor,VEGF)表达的影响。方法:分别用1、5、10μmol/LAs2O3处理AGS细胞,在培养24、48、72h后,以MTT法检测细胞的生长增殖,以流式细胞术和TUNEL法检测细胞凋亡,以ELISA、免疫组化和实时荧光定量PCR检测凋亡过程中相关基因STAT3、VEGF表达的变化。结果:(1)AGS细胞经As2O3作用后,细胞增殖受到明显抑制,且呈剂量和作用时间依赖关系;(2)FCM术检测在细胞周期G1期前出现亚二倍体凋亡峰;细胞周期分析显示G2/M期阻滞;(3)TUNEL标记发现DNA链的断裂;(4)在AGS细胞凋亡过程中,STAT3和VEGF表达下调,其中10μmol/L浓度的As2O3作用最强。结论:As2O3抑制胃癌细胞AGS增殖并诱导凋亡,其机制可能与细胞周期阻滞和下调STAT3和VEGF基因表达有关。

As_2O_3诱导人肾癌786-0细胞凋亡及其分子机制的研究

目的探讨三氧化二砷(As2O3)诱导786-0细胞凋亡的作用及其分子机制。方法用FCM和TUNEL等方法观察As2O3诱导786-0细胞凋亡,以ICC、RT-PCR、ISH、Western blot和EMSA技术等检测凋亡相关基因p53、bcl-2、c-myc、c-fos、NF-κBp65的mRNA和蛋白表达及NF-κBDNA结合活性的改变。结果2μmol/L以上浓度As2O3作用786-0细胞24h后开始发生细胞凋亡,出现凋亡的形态学改变和特征性亚二倍体峰(凋亡峰),使786-0细胞内p53活性升高(P<0.05),而bcl-2、c-myc、c-fos和NF-κBp65基因表达降低(P<0.05),NF-κBDNA结合活性也被显著抑制(P<0.01)。结论As2O3可能通过降低NF-κBp65基因表达和NF-κBDNA结合活性,下调bcl-2、c-myc和c-fos基因表达,而增加p53基因的表达,诱导人肾癌786-0细胞凋亡。