丹参多酚酸盐体外抗肿瘤作用研究

目的:研究丹参多酚酸盐体外抗肿瘤的作用,探讨其可能机制。方法:采用MTT比色法测定注射用丹参多酚酸盐体外对人肝癌细胞株SMMC-7721细胞、人肺腺癌细胞株SPC-A-1细胞、B淋巴瘤细胞株Raji细胞和急性粒细胞白血病细胞株HL-60细胞4种肿瘤细胞株增殖的影响;采用流式细胞仪检测细胞周期的改变及细胞凋亡情况;采用吉姆萨染色及吖啶橙荧光染色观察细胞形态变化。结果:注射用丹参多酚酸盐对SMMC-7721、SPC-A-1、Raji、HL-60细胞增殖均有显著的抑制作用,且呈时间和剂量依赖关系;可诱导SMMC-7721细胞阻滞于S期继而发生细胞凋亡;可观察到细胞逐渐凋亡形态。结论:注射用丹参多酚酸盐有较强的体外抗肿瘤作用,可能是通过作用于细胞周期、诱导肿瘤细胞凋亡来发挥的。     

Redifferentiation of human hepatoma cell induced by 6-(p-chlorophenyl)-3-[1-(p-chlorophenyl)-5-methyl-1 H-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole (TDZ)

6-(p-Chlorophenyl)-3-[1-(p-chlorophenyl)-5-methyl-1 H-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazole (TDZ) is a derivative of various substituted s-triazolo[3,4-b]-1,3,4-thiadiazoles, which are associated with diverse pharmacological activities. However, the antitumor activity of TDZ is not well understood. To evaluate its role on tumor cell lines, we have examined the effect of TDZ on two tumor lines: human hepatoma cell (SMMC-7721) in vitro and Sarcoma180 tumor (S180) in vivo. The cytotoxicity of TDZ on human hepatoma cells was assessed using the MTT assay. The inhibition on tumor growth was evaluated by means of trypan blue exclusion test in vitro, and using a Sarcoma180 tumor (S180) animal model in vivo. A scanning electronic microscope was used to discover the morphological changes on cell surface, cell electrophoresis was employed to determine the changes of cell surface negative charges, and alpha-fetoprotein was applied as a biomarker of hepatoma. The effect of TDZ on DNA synthesis was determined by a [3H]-thymidine incorporation assay, and cell cycle distribution by flow cytometry. The IC50 value of TDZ on SMMC-7721 cells was 52.9 microg/ml (48 h). However, TDZ could inhibit the growth of SMMC-7721 cells at concentrations far lower than the IC50 value. Treated with the same low concentrations of TDZ, microvilli on the surface of SMMC-7721 cells decreased obviously, electrophoresis rate of cells reduced from 2.14 microm ms(-1) x V(-1) x cm(-1) of control to 1.54 and 1.56 microm x s(-1) x V-1 x cm(-1), the content of AFP dropped from 205.14 +/- 6.41 ng x mg(-1) Pr to 115.68 +/- 3.47 and 78.57 +/- 2.35 ng mg(-1) Pr, and the DNA replication was inhibited by 26.8% and 45.2%. These results indicated that TDZ may inhibit proliferation of cancer cells by reversing SMMC-7721 cells malignant phenotypic characteristics and inducing redifferentiation. Flow cytometry showed that TDZ-treated cells resulted in a higher proportion of cells in S phase compared with untreated cells, and only when the concentration reached 64 microg/ml, the apoptosis could happen at the rate of 4.2%. Detection of the inhibition of Sarcoma 180 tumor growth in vivo showed that TDZ reduced the tumor weight and 69.08% of the growth was inhibited. TDZ could inhibit the proliferation of tumors in vitro and in vivo; the possible antitumor mechanism might be inducing redifferentiation at a lower dosage on vitro.     

20(S)-原人参二醇对SMMC-7721细胞体内外作用的研究

目的观察不同剂量的20(S)-原人参二醇(Protopanaxadiol,PPD)在体内外对人肝癌细胞株SMMC-7721抗肿瘤作用。方法建立人肝癌裸鼠皮下移植瘤模型,观察20(S)-原人参二醇的肿瘤抑制作用。MTT比色法检测20(S)-原人参二醇对SMMC-7721细胞的增殖抑制作用,Ho-echst33342核染色观察细胞凋亡形态学改变,采用FITC-An-nexinⅤ/PI双染流式细胞术分析凋亡情况,同时检测Caspase-3活性。结果在体内,PPD可抑制SMMC-7721细胞裸鼠异种移植瘤生长;在体外,PPD对SMMC-7721细胞的增殖具有明显的抑制及诱导其凋亡作用,呈时间和剂量依赖性,Hoechst33342核染色可见凋亡小体,同时伴有Caspase-3活性的增加。结论20(S)-原人参二醇在体内外均可抑制SMMC-7721细胞增殖,并诱导其凋亡,其机制可能通过活化Caspase-3诱导细胞凋亡而发挥抗肿瘤作用。     

hTERT反义寡核苷酸对肝癌SMMC-7721细胞株细胞增殖和端粒酶活性的影响

目的研究hTERT基因反义寡核苷酸（ASPSODN）对SMMC-7721细胞端粒酶活性及细胞增殖的影响。方法不同浓度的ASPSODN转染到SMMC-7721细胞株24h和48h后分别采用MTT法、TRAP-ELISA法检测SMMC-7721细胞的增殖活性及端粒酶活性。结果各浓度组的ASPSODN均能降低端粒酶活性,作用24h时,不同浓度均明显受抑,其中0.8μmol/L ASPSODN较0.2μmol/L和0.4μmol/L组抑制作用更明显（P〈0.05）,但再增大浓度抑制作用并不随着增加。作用48h后,抑制作用减弱,低浓度组（0.2、0.4μmol/L）端粒酶活性恢复到正常水平,而高浓度组（0.8、1.0、1.2μmol/L）抑制作用依然明显,端粒酶活性低于60%。MTT法检测显示,不同浓度ASPSODN组对SMMC-7721细胞的生长均有抑制作用,随着浓度的增加,抑制作用明显,但随着时间的延长,抑制作用增加不明显。结论 ASPSODN靶向hTERT能特异性抑制SMMC-7721细胞增殖,明显下调端粒酶活性,hTERT可能成为肝癌治疗的一个靶点。     

美洲大蠊多肽提取物对SMMC-7721细胞凋亡及Bcl-2和Bax蛋白表达的影响

目的：研究美洲大蠊多肽提取物诱导人肝癌细胞SMMC-7721凋亡及其分子机制。方法：采用不同质量浓度的美洲大蠊多肽提取物作用于SMMC-7721,以Cell Counting Kit-8（CCK-8）法检测细胞抑制率;Hoechst33342/PI与Annexin V-FITC/PI双染法相结合检测SMMC-7721细胞的凋亡;蛋白免疫印迹（Western blotting）法检测细胞凋亡相关因子Bcl-2和Bax蛋白表达。结果：不同质量浓度的美洲大蠊多肽提取物可抑制SMMC-7721细胞的增殖,诱导其凋亡,呈一定的量效关系;Western Blot法显示Bax表达增多,Bcl-2蛋白表达减少,Bcl-2/Bax比值降低。结论：美洲大蠊多肽提取物可明显诱导SMMC-7721细胞凋亡,抑制其增殖,其机制可能与下调Bcl-2蛋白表达,上调Bax蛋白表达,降低Bcl-2/Bax比值有关。     

Study on anti-hepatocarcinoma activity of tectorigenin from Pueraria Flos in vitro

Objective To evaluate the inhibitory effect of tectorigenin on the proliferation of human hepatoma cells SMMC-7721.Methods Tectorigenin was added into SMMC-7721 human hepatoma cells in log phase.After 24 hours the morphologic change was observed with an inverted microscope.The inhibitory effect on the proliferation of tumor cells was evaluated by MTT.The early and late apoptosis rate were measured by flow cytometry using Annexin V-FITC /PI double staining and PI single staining respectively.Results After cultivated with tectorigenin for 24 hours,the hepatoma cells became smaller,rounder and thicker.The adherent cells in experimental group were much fewer.The results of MTT showed that tectorigenin could inhibit the cell proliferation in a concentration-dependence manner from 1.00 μg·mL-1 to 8.00 μg·mL-1.48-hour maximal inhibition rate could reach 76.57%,IC50 was(3.71±1.17)μg·mL-1(n=5).The 6-hour early apoptosis rate of hepatoma cells was(28.05±1.72)%,(56.17±2.14)% and(88.54±3.04)% respectively after cultivated with 5.00,10.00 and 20.00 μg·mL-1 tectorigenin.There were significant difference between the experimental groups and control group whose early apoptosis rate was(6.77±0.81)%(P<0.01).The 48-hour late apoptosis rate was(9.33±0.85)%,(17.02±1.38)% and(38.04±2.03)% respectively,there were also significant difference between the experimental groups and control group(P<0.05).Conclusions Tectorigenin has significant inhibitory effect on the proliferation of SMMC-7721 human hepatoma cells within the range of 1.00 to 16.00 μg·mL-1 and the mechansim may be related to promoting apoptosis.     

In vitro effects on proliferation, telomerase activity and apoptosis of an eremophilanoid sesquiterpene from Senecio oldhamianus maxim in cultured human tumor cell lines

8,11-Dioxol-6-en-9alpha, 10alpha-epoxy-8beta-hydroxyeremophilane (HEM), a new eremophilanoid sesquiterpene, was isolated from Senecio oldhamianus Maxim. Its effects of cytotoxicity, telomerase activity, apoptosis and related genes expression in two human tumor cell lines, human hepatoma cells SMMC-7721 and human oophoroma cells HO-8910, were studied. Hydroxycamptothecine (HCPT) was used as a positive control. The IC50 of cytotoxicity by HEM were 24.9 +/- 2.1 and 19.4 1.6 microM in SMMC-7721 and HO-8910 cells respectively, and 0.35 +/- 0.10 and 0.27 +/- 0.08 microM for HCPT. HEM inhibited telomerase activity with the IC50 35.9 +/- 3.2 microM in SMMC-7721 and 25.6 +/- 2.6 microM in HO-8910 cells, while HCPT had no effect on telomerase activity in both tumor cell lines. HEM 20-30 microM induced apoptosis in SMMC-7721 cells from 5.7% to 18.4% and in HO-8910 cells from 7.6% to 67.1%. While HCPT 0.1-0.5 microM induced apoptosis in SMMC-7721 cells from 6.5% to 13.3% and in HO-8910 cells from 9.9% to 30.9%. HEM 30 microM significantly decreased Bcl-2 protein expression to 58.7% in SMMC-7721 and to 57.6% in HO-8910 cells. While HCPT 0.5 microM significantly decreased Bcl-2 protein expression to 64.3% in SMMC-7721 and to 70.0% in HO-8910 cells. HEM 25 microM and 30 microM significantly increased P53 protein expression 2.3-3.6-fold in SMMC-7721 and 3.0-5.7- fold in HO-8910 cells. While HCPT 0.5 microM significantly increased P53 protein expression 3.3-fold in SMMC-7721 and 2.7-fold in HO-8910 cells. Overall, HCPT exhibited a more potent effect on cytotoxicity and apoptosis in the two tumor cell lines than HEM did. However HEM can inhibit telomerase activity in the two tumor cell lines but HCPT cannot.     

复尔康注射液对人肝癌细胞株及裸鼠移植瘤的抑制作用

目的:研究复尔康注射液对人肝癌细胞株增殖及裸鼠移植瘤生长的影响。方法:采用CCK8试剂盒检测复尔康注射液对人肝癌细胞株SMMC-7721和BeL-7402增殖的抑制作用;建立SMMC-7721细胞裸鼠移植瘤模型,通过比较肿瘤体积(tumor volume,TV)、相对肿瘤体积(relative tumor volume,RTV)和相对肿瘤增殖率(T/C)考察复尔康注射液对肿瘤生长的影响。结果:复尔康注射液对SMMC-7721和BeL-7402的IC50分别为(61.51±1.58),(68.39±7.16)mg·L-1;不同剂量复尔康注射液能够不同程度地抑制裸鼠移植瘤的生长,与阴性对照组比较,P<0.05。低、中、高剂量复尔康注射液组(0.065,0.130,0.260 g·kg-1)T/C分别为57.75%,39.9%和44.08%。结论:复尔康注射液体外能抑制人肝癌细胞株的增殖,体内能明显抑制SMMC-7721细胞裸鼠移植瘤的生长。     

维A酸注射液对人肝癌细胞SMMC-7721及其裸小鼠移植瘤的抑制作用

目的:研究维A酸注射液对人肝癌细胞SMMC-7721增殖的抑制作用及其对裸鼠移植瘤生长的影响。方法:采用细胞计数试剂盒检测不同浓度维A酸注射液对SMMC-7721细胞增殖的抑制作用,计算半数抑菌浓度(IC50)。建立裸鼠SMMC-7721移植瘤模型,分为阴性对照组(n=12)、阳性对照(顺铂1mg.kg-1)组和维A酸低、中、高剂量(7.5、15、30mg.kg-1)组,后4组各6只。腹腔给予相应药物,每周连续给药5d后停药2d,共给药4周,每周检测各组裸小鼠体重、肿瘤体积(TV)、相对肿瘤体积(RTV)、相对肿瘤增殖率(T/C),及末次给药2d后移植瘤组织中凋亡细胞阳性率和半胱氨酸蛋白酶3(Caspase-3)的表达。结果:维A酸注射液对SMMC-7721细胞的IC50为(15.14±0.46)μg.mL-1。小鼠给药19d(治疗疗效最佳时间)时,与阴性对照组比较,其余各组TV、RTV均明显下降(P<0.05或P<0.01),体重无明显变化,T/C均小于60%;末次给药2d后,与阴性对照组比较,维A酸3个剂量组凋亡细胞阳性率和Caspase-3表达明显升高(P<0.05或P<0.01)。结论:维A酸注射液能抑制SMMC-7721细胞的增殖及其裸小鼠移植瘤的生长,其机制可能与促进细胞凋亡和Caspase-3表达有关。     

The cytotoxicity induced by brucine from the seed of Strychnos nux-vomica proceeds via apoptosis and is mediated by cyclooxygenase 2 and caspase 3 in SMMC 7221 cells.

To study the cytotoxicity of four alkaloids: brucine, strychnine, brucine N-oxide and isostrychnine from nux vomica on SMMC 7721 cells and their possible mechanisms, MET assay was used to examine the growth inhibitory effects of these alkaloids. Brucine revealed the strongest growth inhibitory effect on SMMC-7721 cells. Furthermore, as directly observed under an inverted microscope, fluorescent microscope and transmission electronic microscope, brucine caused SMMC-7721 cell shrinkage, membrane blobbing, formation of apoptotic body as well as nucleus condensation, all of which are typical characteristics of apoptotic programmed cell death. In addition, brucine dose-dependently caused SMMC-7721 cells apoptosis via formation of subdipolid DNA and phosphatidylserine externalization, as evidenced by flow cytometry analysis. The brucine-induced apoptosis was partially attributed to the activation of caspase 3 as well as cyclooxygenase 2 inhibition, since neither caspase 3 specific inhibitor, z-DEVD-fmk nor was exogenous addition of prostaglandin E(2) able to completely abrogate the brucine-induced SMMC 7721 cell apoptosis. In sum, this paper indicate that the major alkaloids present in the seed of Strychnos nux-vomica are effective against SMMC-7721 cells proliferation, among which brucine proceeds SMMC-7721 cells death via apoptosis, probably through the participation of caspase 3 and cyclooxygenase 2.     

黄连解毒汤体内外抗肿瘤作用的实验研究

目的：观察黄连解毒汤的体内、体外抗肿瘤作用。 方法：采用小鼠肉瘤S180和小鼠前胃癌MFC等移植性肿瘤模型进行体内实验,通过检测抑瘤率、胸腺指数、脾脏指数等指标观察黄连解毒汤的体内抑瘤作用及对免疫器官的影响。并用MTT方法检测黄连解毒汤对小鼠S180、小鼠MFC、人胃癌SGC-7901、人肝癌SMMC-7721等4种瘤株的抑制作用。结果：黄连解毒汤大、中剂量组中对S180荷瘤小鼠有抑制作用,大剂量组对MFC荷瘤小鼠有抑制作用,抑瘤率分别为48.38%、33.77%、30.74%;对S180、MFC、SGC-7901和SMMC-7721细胞均有一定的细胞毒作用, IC50分别为99.73 mg?L-1、84.47 mg?L-1、153.32 mg?L-1和102.87 mg?L-1。结论：黄连解毒汤体内对S180、MFC小鼠移植瘤有一定的抗肿瘤活性,体外对4种肿瘤细胞也具有抑制作用。     

绵毛胡桐内酯对人口腔上皮癌KB细胞端粒酶的影响

目的:探讨绵毛胡桐内酯(Calanolide)对KB细胞生长抑制作用及其对端粒酶活性和细胞周期的影响。方法:采用四甲基偶氮唑蓝(MTT)法检测Calanolide对体外培养的KB细胞增殖的抑制作用,TRAP-PCR-ELISA方法检测在Calanolide作用后KB细胞端粒酶活性的变化,用流式细胞仪分析细胞周期的改变。结果:Calanolide在10~50mg/L剂量范围内对KB细胞有抑制作用,且呈剂量依赖关系(P<0.05);Calanolide作用后端粒酶活性出现抑制,且各给药组随Calanolide浓度增加抑制作用显著增强(P<0.01),同一浓度随作用时间延长,抑制作用逐渐增强(P<0.05);KB细胞的G2/M期细胞含量明显增高(P<0.01)。结论:Calanolide对肿瘤细胞的端粒酶活性有抑制作用。     

Anticancer effect of two diterpenoid compounds isolated from Annona glabra Linn

INTRODUCTION Traditional Chinese medicine afforded a valuableapproach in the searching for new anticancer drugs.Studies on the pharmacological mechanism and search-ing for new chemical structures from herbal extractfor new anticancer drugs caught great interest[1]. Taxol,isolated from the stem bark of Taxus brevifolia, pro-vided a typical example in this respect. Taxol was rankedas “the most important new drug we have had in can-cer for 15 years”[2]. Annonaceous acetogenius were …     

新型金属铜络合物对SMMC-7721细胞增殖与凋亡的影响

目的研究新型金属铜络合物(N-Cu)在体外对人肝癌SMMC-7721细胞增殖与凋亡的影响及其作用机制。方法将不同浓度的N-Cu(0.3～24μmol.L-1)作用于体外培养的SMMC-7721细胞,应用MTT法检测细胞生长抑制率,FCM法检测细胞周期及凋亡率,RT-PCR和Western blot法检测细胞中Bcl-2、Bax、Caspase-3 mRNA和蛋白表达的变化。结果 N-Cu可明显抑制SMMC-7721细胞的增殖,呈明显的量效与时效关系。随着药物浓度的增加,G0/G1期的细胞比率上升,G2/M和S期细胞比率下降,并促进凋亡率增加。N-Cu可上调细胞中Bax、Caspase-3基因及蛋白的表达,抑制Bcl-2基因及蛋白的表达,且均呈剂量依赖性。结论一定浓度的N-Cu可抑制SMMC-7721细胞的增殖并诱导其凋亡,阻滞细胞周期于G0/G1期。上调Bax、Caspase-3基因及蛋白的表达,降低Bcl-2/Bax比值,可能是其诱导细胞凋亡的重要机制。     

三磷酸腺苷对国人食管癌Eca-109和肝癌SMMC-7721细胞增殖的影响

目的研究三磷酸腺苷(ATP)对人食管癌细胞株Eca-109和人肝癌细胞株SMMC-7721细胞增殖的影响。方法采用MTT法测定ATP、腺苷(ADO)和三磷酸尿苷(UTP)抑制肿瘤细胞增殖的作用,W rights-G iem sa染色观察细胞形态学的改变。结果ATP(0.03~0.3 mmol.L-1)和ADO(0.1~0.3 mmol.L-1)可不同程度地抑制Eca-109和SMMC-7721的增殖,ATP对两株肿瘤细胞增殖的抑制作用均强于ADO。ATP和ADO对Eca-109细胞的最大抑制率分别为86.36%和29.88%,IC50分别为0.056和0.823 mmol.L-1;对SMMC-7721细胞的最大抑制率分别为82.06%和52.84%,IC50分别为0.218和0.517 mmol.L-1。UTP对Eca-109细胞有很弱的抑制增殖作用,最大抑制率仅为18.27%;对SMMC-7721无抗增殖作用。两株细胞经高浓度(0.3 mmol.L-1)ATP处理后,部分SMMC-7721细胞形态出现了明显的凋亡特征,而Eca-109细胞凋亡特征不明显。结论ATP具有较强的抗Eca-109细胞增殖作用,其抗增殖作用主要由ATP自身所致,代谢产物ADO也具有一定的作用;而对于SMMC-7721细胞,ATP可能较大程度地通过降解为ADO而发挥抗增殖作用。     

螺旋藻多糖硫酸酯化修饰前后抗肿瘤及免疫活性的研究

比较螺旋藻多糖硫酸酯化修饰前后体内外抗肿瘤及免疫活性.采用MTT比色法研究药物在体外对人肿瘤细胞株的抑制作用,促进正常小鼠脾淋巴细胞的增殖活性以及对荷瘤小鼠NK和CTL细胞活性的影响.采用移植性肿瘤实验方法考察了药物对小鼠S180肉瘤的抑制作用.结果显示,螺旋藻多糖（NPSP）对肿瘤细胞株几乎无细胞毒作用,硫酸酯化螺旋藻多糖（SNPSP）对肿瘤细胞株具有显著的细胞毒作用,其中对SMMC-7721人肝癌细胞株抑制率最高达50%.NPSP50 mg/kg对小鼠S180肉瘤无抑制,相同剂量的SNPSP对小鼠S180肉瘤的抑制率达35.42%.NPSP具有促进脾淋巴细胞增殖作用,但对ConA和LPS诱导的脾淋巴细胞增殖反应无促进作用,SNPSP促进脾淋巴细胞增殖作用较NPSP增强,同时对ConA和LPS诱导的脾淋巴细胞增殖反应也具有明显的促进作用.NPSP和SNPSP均能促进荷瘤小鼠NK细胞和CTL细胞活性,其中SNPSP促进CTL细胞活性较NPSP增强.     

白藜芦醇对人肝癌细胞株SMMC-7721增殖和凋亡的影响

目的观察白藜芦醇对人肝癌细胞株SMMC-7721增殖和凋亡的影响,并初步探讨其机制。方法用MTT法检测白藜芦醇对SMMC-7721细胞增殖影响的量效与时效关系;应用流式细胞术（FCM）检测细胞凋亡率;比色法测定caspase-3酶活性。结果白藜芦醇（50、100、200μmol·L^-1）处理SMMC-7721细胞48h,呈浓度依赖性抑制SMMC-7721细胞增殖且诱导其凋亡;100μmol·L^-1白藜芦醇处理细胞24、48或72h显著抑制SMMC-7721细胞增殖并诱导其凋亡,且呈时间依赖性。白藜芦醇（50、100、200μmol·L^-1）处理SMMC-7721细胞48h,呈浓度依赖性增加SMMC-7721细胞caspase-3活性。结论白藜芦醇可抑制人肝癌细胞株洲C-7721的增殖,诱导细胞凋亡,其机制与增强细胞内caspase-3活性有关。     

富硒蚕蛹氨基酸诱导人肝癌细胞SMMC-7721凋亡的研究

目的　研究富硒蚕蛹氨基酸对人肝癌细胞SMMC 772 1的作用。方法　以人肝癌细胞SMMC 772 1为模型 ,采用原子荧光分光光度计测定蚕蛹硒含量 ,通过噻唑蓝(MTT)比色法检测细胞生长及活力 ,用倒置荧光显微镜观察细胞形态学变化 ,流式细胞仪研究细胞的凋亡及细胞周期变化。结果　①陕西紫阳县蚕蛹中硒的含量为普通蚕蛹硒含量的 2 15倍 ,②富硒蚕蛹氨基酸在 0 5、1 5和 2 5 μmol·L-1硒浓度下能显著性抑制肝癌细胞生长 ,并具有浓度和时间依赖性。亚硒酸钠对细胞生长的抑制作用不如富硒蚕蛹氨基酸。相反 ,普通蚕蛹氨基酸促进细胞的生长。③富硒蚕蛹氨基酸作用于细胞后 ,倒置荧光显微镜观察到细胞形态学变化及细胞存活率降低。④流式细胞仪检测到 0 5、1 5和2 5 μmol·L-1富硒蚕蛹氨基酸所致细胞凋亡及细胞周期的变化 ,该氨基酸能阻滞SMMC 772 1的细胞周期于G2 /M期 ,使G2 /M期细胞比例增加 ,而G0 /G1期细胞比例下降。结论　富硒蚕蛹氨基酸能诱导SMMC 772 1细胞的凋亡 ,其抗癌机制可能与其改变细胞周期进而诱导细胞凋亡相关联。     

Synergic effect of 3'-azido-3'-deoxythymidine and arsenic trioxide in suppressing hepatoma cells

The aim of this study was to investigate the synergic antitumor effects of arsenic trioxide (As2O3) and 3'-azido-3'-deoxythymidine (AZT) on hepatoma cells and explore the possible molecular basis of these effects. These results showed that AZT enhanced the inhibitory effect of As2O3 on HepG2 and SMMC-7721 cell growth. The IC50 of As2O3 in combination with AZT was lower than that of As2O3 alone. A concentration-dependent synergic effect of As2O3 and AZT (CI < 1) was observed in all the tested combinations of these compounds. These results also showed that the combination of As2O3 and AZT dramatically and significantly increased the number of apoptotic cells in HepG2 and SMMC-7721 cells. Studies in vivo showed that the combination of As2O3 and AZT was statistically superior to either As2O3 or AZT alone in the treatment of tumor-bearing mice. As2O3 (1 mg/kg) containing AZT (50 mg/kg) inhibits proliferation of implanted hepatoma 22 by 56.35%. These results suggest that treating hepatoma with a combination of As2O3 and AZT offers the advantages of reduced toxic side effects and improved therapeutic efficacy. To understand the mechanism through which As2O3 and AZT suppress tumors, we studied the effects of these compounds, both separately, and in combination, on telomerase and caspase-3 activity. The results showed that the growth inhibitory and apoptotic effects of As2O3 and AZT on human hepatoma cells could be related to the inhibition of telomerase and the activation of caspase 3.