顺铂诱导人卵巢癌AO 10/17细胞凋亡的实验研究

目的探讨顺铂是否通过诱导肿瘤细胞凋亡而抑制肿瘤生长,以及细胞凋亡和细胞周期、细胞内外钙离子浓度的关系。方法应用顺铂处理ＡＯ１０／１７细胞,ＨＥ染色观察细胞形态学改变;琼脂糖凝胶电泳观察ＤＮＡ降解,以及应用流式细胞仪观察细胞凋亡过程中细胞周期的改变及细胞内钙离子的变化。结果在顺铂作用下,ＡＯ１０／１７细胞呈凋亡改变,ＤＮＡ琼脂糖凝胶电泳呈典型的凋亡特征。细胞凋亡的同时细胞周期发生特定的改变,细胞内钙离子升高,但用ＣａＣｌ２与顺铂同时处理细胞,没有促进顺铂的作用。结论顺铂通过细胞内钙离子变化,诱导人卵巢癌细胞凋亡,是顺铂抑制卵巢肿瘤生长的机理之一;顺铂诱导的细胞凋亡与细胞周期有关     

Genistein对人卵巢癌细胞系TC-1增殖抑制和诱导凋亡作用的研究

目的:研究植物雌激素染料木黄酮(genistein)对人卵巢癌细胞系TC-1细胞增殖的抑制作用和凋亡的诱导作用,探讨其抗癌作用的机制。方法:应用MTT法检测不同浓度genistein对TC-1细胞的生长抑制作用,电镜观察药物作用后细胞超微结构的改变,流式细胞仪检测细胞周期、定量分析凋亡,DNA琼脂糖凝胶电泳法确定凋亡。结果:TC-1细胞经不同浓度genistein处理后,细胞生长明显受到抑制,且这种抑制作用呈时间及浓度依赖性,5mg/L和10mg/L genistein作用72h后,抑制率分别达到89·84%和97·99%。genistein阻断TC-1细胞生长于G2/M期,在G0/G1前出现典型的亚二倍体凋亡峰,且凋亡呈时间依赖性。电镜观察到用药后凋亡细胞典型的形态学特征。DNA凝胶电泳可观察到细胞凋亡特异的DNA梯形带。结论:genistein对TC-1细胞生长的抑制作用呈明显的时间及浓度依赖性,并诱导其发生凋亡。     

三苯氧胺对人卵巢癌细胞增殖和凋亡的影响

目的：探讨三苯氧胺的不同剂量（0.1、1、10μmol／L）对人卵巢癌细胞增殖和凋亡的影响,为卵巢癌的内分泌治疗提供实验依据。方法：以体外培养人卵巢癌细胞系HO－8910为研究对象,用免疫组化SABC法检测增殖细胞核抗原（PCNA）在细胞中表达情况,DNA缺口原位末端标记方法（TUNEL）检测细胞凋亡。结果：三苯氧胺通过诱导细胞凋亡抑制卵巢癌细胞生长,至剂量依赖性。低浓度（≤1μmol／L）的三苯氧胺对PCNA表达的影响无统计学意义,高剂量（10μmol／L）可明显降低PCNA表达。结论：三苯氧胺抗肿瘤作用与剂量有关,低剂量通过诱导细胞凋亡发挥作用,而高剂量与抑制细胞增殖和诱导凋亡有关。     

Synergistic antitumor effect of tumor necrosis factor–related apoptosis-inducing ligand combined with cisplatin in ovarian carcinoma cell lines in vitro and in vivo

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to exert selectively cytotoxic activity against many tumor cells but not normal cells. In this study, we evaluated the antitumor activity of TRAIL and cisplatin (CDDP) both separately and combined in the human ovarian cancer cell lines. In vitro study showed that TRAIL elicited significant cell apoptosis of cell lines 3AO, SKOV3, and OVCAR3 in a dose- and time-dependent manner (P < 0.05), while normal ovarian epithelial cells were resistant; this toxicity-free effect may be the result of upregulation of TRAIL receptors DcR1 and DcR2. Combined TRAIL and CDDP therapy produced more profound cell killing in 3AO cells than each alone (P < 0.05), and CDDP could upregulate the expression of both death and decoy TRAIL receptors. To further evaluate the apoptosis-inducing effects of TRAIL and the combination therapy, the abdominally and subcutaneously spread tumors in nude mice via inoculation of 3AO cells were established, and treatment of TRAIL resulted in a dose- and time-dependent inhibition of tumor growth while slight damage was observed in normal tissues. Furthermore, combined TRAIL and CDDP therapy had a synergistic effect in the regression of established ovarian cancer xenografts than TRAIL treatment alone (P < 0.05). We also examined the apoptosis-related gene expression in the transplantation tumors after TRAIL treatment, and the data suggested that the intracellular mechanism of TRAIL may be associated with downregulation of Bcl-2 and upregulation of CD95 and Apo2.7.     

卵巢癌细胞诱导T淋巴细胞凋亡的实验研究

目的　探讨卵巢癌细胞诱导T淋巴细胞凋亡及一氧化氮与细胞内游离钙离子在T淋巴细胞凋亡过程中的作用。方法　分别采用电子显微镜、流式细胞仪观察 3个卵巢癌细胞株 (OVCAR3、CAOV3和SKOV3 )的培养上清液诱导的CD+ 8T淋巴细胞的凋亡 ;逆转录 聚合酶链反应 (RT PCR)技术检测诱导型一氧化氮合成酶 (iNOS)mRNA的表达 ;Fura 2荧光负荷技术和酶联免疫 (EIA)法分别检测细胞内游离钙离子浓度 ( [Ca2 + ]i)和环鸟苷酸 (cGMP)浓度。结果　 ( 1)分别经卵巢癌细胞株OVCAR3、CAOV3和SKOV3细胞培养的上清液作用后 ,CD+ 8T淋巴细胞出现典型的凋亡改变 ,即染色质固缩和片段化 ;流式细胞仪上见凋亡峰 ;细胞凋亡率 [分别为 ( 2 3 8± 3 5) % ,( 2 3 1± 2 9) %、( 2 4 2± 4 9) % ]较对照 [( 4 6± 0 5) % ]明显增高 (P <0 0 1) ;( 2 )CD+ 8T淋巴细胞凋亡过程中iNOSmRNA的表达 (分别为 1 14± 0 0 3 ,1 0 5± 0 0 4,1 16± 0 0 2 )较对照 ( 0 60± 0 0 3 )显著增高 (P <0 0 1) ;细胞内游离 [Ca2 + ]i[分别为 ( 3 80± 3 8)、( 3 66± 13 )、( 3 56± 2 0 )nmol L]和cGMP浓度 [分别为 ( 0 65± 0 0 9)、( 0 62± 0 16)、( 0 57± 0 12 )pmol ml]均较对照 [分别为 ( 184± 11)nmol L、( 0 2 9± 0 0 4     

TWEAK调控凋亡增加上皮性卵巢癌细胞对铂类药物敏感性的研究

目的：探讨肿瘤坏死因子样凋亡微弱诱导剂（TWEAK）在调控上皮性卵巢癌（EOC）细胞对顺铂（DDP）敏感性中发挥的作用。方法：不同浓度TWEAK刺激A2780/cDDP细胞后,采用CCK-8法检测细胞的增殖能力及DDP半数抑制浓度（IC50）的变化;采用流式细胞术检测细胞凋亡率的变化;采用透射电镜检测细胞核染色质形态和凋亡小体的变化;Western blot法检测细胞凋亡相关蛋白caspase 3的活化情况。结果：TWEAK对A2780/cDDP细胞的增殖能力无影响,但能显著增加A2780/cDDP细胞对DDP的敏感性。流式结果显示,随着TWEAK剂量增加,A2780/cDDP细胞的凋亡显著增加。TWEAK刺激后A2780/cDDP细胞中caspase 3活化体表达增加,细胞核染色质发生形态变化,诱导了细胞的凋亡及凋亡小体形成。结论：TWEAK通过活化凋亡相关通路,促进EOC细胞凋亡,提高了DDP耐药EOC细胞对DDP的敏感性。这可能为临床开创逆转EOC铂类耐药的治疗新途径提供理论依据。     

活性半胱氨酸天冬氨酸蛋白酶3分子的构建及其致卵巢上皮性癌细胞凋亡的实验研究

目的 构建能自我激活的活性半胱氨酸天冬氨酸蛋白酶(caspase)3分子,并探讨其对卵巢上皮性癌(卵巢癌)细胞的致凋亡作用.方法利用基因重组技术构建活性caspase-3分子--rev-caspase-3及其重组腺病毒--Ad-rev-casp3;应用免疫组化方法、细胞计数试剂盒8、流式细胞仪和蛋白印迹法分别检测rev-caspase-3作用后卵巢癌细胞系AO细胞中活性caspae-3蛋白的表达情况、细胞存活率、凋亡率、细胞周期、caspase-3活性亚单位p17和聚(腺苷二磷酸-核糖)多聚酶(PARP)的分解产物p85的表达水平,应用透射电镜观察rev-caspase-3作用后细胞的超微结构,实时PCR技术检测细胞中凋亡相关基因的表达情况;建立卵巢癌裸鼠皮下及腹腔移植瘤模型,观测rev-caspase-3作用后裸鼠生存情况及肿瘤体积的变化.结果 Ad-rev-casp3作用后的AO细胞中显著表达活性caspase-3蛋白,细胞质明显棕染;细胞中活性caspase-3亚单位p17和PARP裂解片段p85的表达水平升高.Ad-rev-casp3以感染复数(MOI)为70作用后的AO细胞存活率为30.3%,凋亡率为40.2%.Ad-rev-casp3以MOI=10作用后的细胞凋亡率只为3.4%,但此时S期细胞比例高达56.5%,G1期比例下降至9.8%,与未感染Ad-rev-casp3(MOI=0)的AO细胞的S期和G1期比例显著不同(P均＜0.05).Ad-rev-casp3作用后的AO细胞呈现显著的凋亡形态改变,电镜下见明显的凋亡小体形成;细胞中活性caspase-3基因的表达水平显著升高,为9.44.Ad-rev-casp3能显著延长荷瘤裸鼠的生存期,平均生存时间为(213±16)d,并显著抑制移植瘤的生长,在第1次注射后53 d时抑瘤率为70%.结论 表达rev-caspase-3的重组腺病毒载体对卵巢癌细胞有强烈的致凋亡作用,并可显著延长荷瘤裸鼠的生存期,抑制肿瘤生长.     

溶血磷脂酸抑制顺铂诱导卵巢癌细胞凋亡机制的研究

目的:探讨溶血磷脂酸(LPA)抑制顺铂(DDP)诱导卵巢癌细胞凋亡的机制。方法:体外培养人卵巢上皮癌细胞株SKOV3,选用促分裂素原活化蛋白激酶(MAPK)信号传导通路特异性阻断剂PD98059,应用四甲基偶氮唑蓝(MTT)比色法测定DDP、DDP+LPA和DDP+LPA+PD98059对SKOV3细胞增殖活性的影响;应用Ho-echst33258荧光染色观察凋亡细胞;应用实时荧光定量PCR(RT-PCR)测定单用LPA或合用PD98059对SKOV3细胞环氧化酶-2(COX-2)表达的影响;应用流式细胞仪(FCM)测定细胞凋亡及细胞周期的变化。结果:LPA对DPP抑制卵巢癌细胞增殖有拮抗作用,且增加S期细胞比率;联合应用PD98059后,卵巢癌细胞生长受抑制,S期比率降低,而凋亡小体产生增多。RT-PCR结果显示,LPA能促进COX-2表达(P<0.05),而合用PD98059后COX-2表达降低(P<0.05)。结论:LPA通过MAPK信号传导通路抑制顺铂诱导的卵巢癌细胞凋亡,且与COX-2表达有关。     

应用AnnexinV-FITC/PI-FCM定量分析对5-FU诱导卵巢癌细胞系凋亡的研究

目的　应用AnnexinV -FITC/PI -FCM定量分析 5 -氟尿嘧啶 (5 -FU)诱导卵巢癌细胞系OVCAR发生的凋亡。方法　将 5 -FU以 0、2 0mg/L、10 0mg/L、2 0 0mg/L的浓度 ,分别处理OVCAR细胞 12、2 4、48小时 ,然后用形态学观察、DNA琼脂糖电泳和AnnexinV -FITC/PI流式细胞技术 (flowcytometric,FCM)检测其诱发凋亡的情况。结果　AnnexinV -FITC -FCM分析见 ,随 5 -FU作用浓度增加、时间延长 ,凋亡细胞比例明显升高 ,差异显著 (P <0 .0 1) ,继发性坏死细胞比例增加 ,差异明显 (P <0 .0 5 )。结论　 5 -FU可以诱发OVCAR细胞发生凋亡 ,应用AnnexinV -FITC/PI -FCM能对细胞凋亡定性的同时测出活细胞、凋亡细胞、继发性坏死细胞和培养操作过程中出现机械损伤细胞的比例 ,与传统方法相比 ,更能直观、准确地反映细胞凋亡与药物浓度及处理时间的关系     

可溶型Fas在卵巢肿瘤中的表达及其生物学意义分析

目的　检测Fas基因在各类人卵巢组织标本和卵巢癌细胞系中的表达并分析其对肿瘤发生的意义。方法　应用免疫组织化学染色和Western印迹杂交技术 ,对 8例非瘤卵巢组织、18例良性和 2 3例卵巢癌标本以及 3株卵巢癌细胞系中Fas基因的表达情况加以分析 ,观察抗Fas抗体对卵巢癌细胞体外生长的影响。结果　Fas在非瘤卵巢组织中的阳性表达率是 12 5 % ,在良性肿瘤为 89% ,在浆液性囊腺癌和粘液性囊腺癌分别为10 0 %和 86 % ;3株卵巢癌细胞系Fas均呈阳性表达。Western印迹杂交显示 :卵巢癌细胞产生的Fas蛋白以分子质量 40ku的可溶型 (sFas)为主 ,伴少 (痕 )量的 43ku膜型 (mFas)。用最高浓度为 2 0 0 μg/L的抗Fas抗体处理 3株卵巢癌细胞系 ,未能抑制靶细胞生长和诱导凋亡。结论　sFas普遍存在于卵巢肿瘤和癌细胞系。缺乏mFas可能是影响卵巢癌细胞凋亡和 (或 )化疗耐受性的遗传学因素之一     

维生素E琥珀酸酯诱导卵巢癌细胞SKOV3凋亡的研究

目的探讨维生素E琥珀酸酯(Vitamin E Succinate,VES)对人卵巢腺癌细胞系SKOV3的生物学效应及机制.方法依培养基中有无加VES,将培养的SKOV3细胞分为对照组和实验组,通过MTT比色法检测VES对该细胞系杀伤率的影响;通过光学显微镜、透射电镜观察及流式细胞仪分析检测凋亡;利用caspase-3荧光检测探讨VES作用、SKOV3细胞的作用机制.结果VES处理SKOV3细胞后,细胞存活率明显降低,光镜下见明显形态学改变,电镜下见各个时期的凋亡细胞,流式细胞仪测定发现典型的凋亡峰,活性caspase-3荧光强度增加.结论VES能诱导卵巢腺癌SKOV3凋亡并可能通过激活caspase家族实现.     

紫杉醇诱导卵巢癌细胞凋亡及对survivin基因表达的影响

目的 :观察紫杉醇对人卵巢癌细胞系A2 780凋亡的作用 ,探讨其对卵巢癌细胞survivin基因表达的影响。方法 :应用MTT、流式细胞仪等方法研究紫杉醇对卵巢癌细胞系A2 780凋亡的诱导作用 ,运用RT- PCR分析紫杉醇对卵巢癌细胞survivin表达的影响。结果 :紫杉醇可诱导卵巢癌细胞系A2 780凋亡 ,不同浓度的紫杉醇引起的凋亡率不同 ,在紫杉醇浓度≥ 10 - 7mol.L- 1时 ,凋亡率显著升高。经紫杉醇作用后的卵巢癌细胞表达sur vivin较用药前明显下降。结论 :紫杉醇可能通过抑制survivin的表达 ,促进肿瘤细胞凋亡。     

Correlation between soluble Fas level and apoptosis of T cells in ovarian carcinoma

OBJECTIVES: The objectives were to examine the correlation between soluble Fas (sFas) level and apoptosis of T cells in peripheral blood and peritoneal fluid of patients with ovarian carcinoma and to investigate the possible sFas effect on T cell apoptosis. STUDY DESIGN: Patients with stages I-II ovarian carcinoma (n=10) and patients with stages III-IV ovarian carcinoma (n=22), as well as ovarian benign tumors (n=8), were enrolled in the study. Apoptosis of and Fas expression on T cells from peripheral blood and peritoneal fluids were assessed by flow cytometry. Soluble Fas level was assayed using an ELISA kit. The effects of peritoneal fluid on Jurkat cell apoptosis with or without depletion of sFas were evaluated and compared in vitro. RESULTS: The sFas level and apoptosis of T cells in peripheral blood and peritoneal fluid from stages III-IV ovarian carcinoma were significantly higher than those from stages I-II ovarian carcinoma (p<0.01 in all instances) and benign ovarian tumor (p<0.01 in all instances). In peritoneal fluid, the sFas level and apoptosis of T cells from stages I-II ovarian carcinoma were significantly higher than those from benign ovarian tumor (p<0.01 in all instances), and the Fas expression on T cells from ovarian carcinoma were higher than those from benign ovarian tumor (p<0.05 in all instances). There was a positive correlation between the sFas level and the apoptosis of T cells in peritoneal fluids from stages III-IV ovarian carcinoma (r=0.647, p=0.001). Peritoneal fluid of ovarian carcinoma could induce significant Jurkat cell apoptosis. The blocking of Fas expression on the Jurkat cell surface, but not the deletion of sFas, may remarkably restrain the apoptosis level. CONCLUSIONS: Elevated sFas is correlated with apoptosis of T cells in peripheral blood and peritoneal fluid from ovarian carcinoma. Soluble Fas evidently does not affect T cell apoptosis, which is probably due to elevated Fas expression on T cells.     

Costunolide induces apoptosis in platinum-resistant human ovarian cancer cells by generating reactive oxygen species

Objective

The acquired resistance to platinum-based drugs has become an obstacle in the management of ovarian cancer. We investigated the apoptosis-inducing effect of costunolide, a natural sesquiterpene lactone, in platinum-resistant human ovarian cancer cells, along with the molecular mechanism of action.

Methods

Costunolide and cisplatin were examined in platinum-resistant human ovarian cancer cells. MTT assay for cell viability, PI staining for cell cycle profiling, and Annexin V assay for apoptosis analysis. ROS production and protein expression was assessed by H₂DCFDA staining and Western blotting, respectively. Combination effect was determined using the Combination Index (CI) method.

Results

It was found that costunolide is more potent than cisplatin in inhibiting cell growth in three platinum-resistant ovarian cancer cell lines (MPSC1^PT, A2780^PT, and SKOV3^PT). Costunolide induced apoptosis of platinum-resistant cells in a time- and dose-dependent manner and suppressed tumor growth in SKOV3^PT-bearing mouse model. In addition, costunolide triggered the activation of caspase-3, -8, and -9. Pretreatment with caspase inhibitors neutralized the pro-apoptotic activity of costunolide. We further demonstrated that costunolide induced a significant increase in intracellular reactive oxygen species (ROS). Additionally, the antioxidant N-acetyl-L-cysteine (NAC) significantly attenuated the costunolide-induced production of ROS, activation of caspases, down-regulation of Bcl-2, and apoptosis in platinum-resistant ovarian cancer cells. Moreover, costunolide synergized with cisplatin to induce cell death in platinum-resistant ovarian cancer cells.

Conclusions

Taken together, these data suggest that costunolide, alone or in combination with cisplatin, may be of therapeutic potential in platinum-resistant ovarian cancer.     

3-甲基腺嘌呤对顺铂诱导卵巢癌细胞凋亡影响的研究

目的:探讨自噬抑制剂3-甲基腺嘌呤(3-MA)对顺铂(DDP)诱导的卵巢癌SKOV3细胞凋亡的影响。方法:体外培养卵巢癌SKOV3细胞,用PI3K/Akt通路抑制剂3-MA预处理SKOV3细胞3h,再用DDP作用48h,经Annexin V-FITC/PI双染色流式细胞仪检测凋亡率,TUNEL法检测凋亡指数(AI),Western blot检测凋亡蛋白caspase3,caspase9的表达。结果:3-MA预处理后,DDP诱导的卵巢癌SKOV3细胞凋亡率为(37.04±7.15)%,凋亡指数为58.0±5.20,而单用DDP组凋亡率为(10.46±0.65)%,凋亡指数为26.0±3.46。3-MA预处理后,DDP诱导的SKOV3细胞凋亡率和凋亡指数均较单用DDP组明显提高(P<0.05)。caspase3,caspase9蛋白的表达也明显增强。结论:3-MA可上调caspase3,caspase9蛋白的表达,通过内源性途经增强DDP促卵巢癌细胞SKOV3的凋亡活性。     

紫花牡荆素体外抑制人卵巢癌HO-8910细胞增殖和诱导凋亡的研究

目的:探讨紫花牡荆素(casticin)体外抑制人卵巢癌HO-8910细胞增殖和诱导凋亡的效应及其机制。方法:MTT法检测casticin对人卵巢癌HO-8910细胞增殖的抑制;Hoechest33258染色观察细胞凋亡形态学改变;流式细胞术(FCM)检测casticin处理HO-8910细胞的凋亡率;Western blotting分析caspase-3、CyclinB1、p21蛋白表达变化。结果:casticin对人卵巢癌HO-8910细胞增殖有较强的抑制作用,呈剂量和时间依赖性。经casticin作用48h后HO-8910细胞表现出典型的凋亡形态特征,并剂量依赖性地增加亚二倍峰,降低CyclinB1蛋白表达,增高caspase-3和p21表达。结论:casticin通过降低CyclinB1表达、活化p21和caspase-3抑制HO-8910细胞增殖并诱导凋亡。     

微小RNA-21表达在卵巢癌细胞生长和凋亡过程中的作用

目的;探讨微小RNA-21( miR-21)在卵巢癌细胞生长、凋亡中的作用及调节机制。方法构建表达miR-21的重组干扰载体pSIREN-miR-21质粒,采用酶切鉴定和测序法证实。实验分为3组,即转染组：卵巢癌细胞株OVCAR3细胞转染重组干扰载体pSIREN-miR-21质粒;阴性对照组：OVCAR3细胞转染阴性对照pSIREN-miR-21-Neg质粒;空白对照组：OVCAR3细胞不转染质粒。采用茎环实时荧光定量逆转录(RT)-PCR技术检测3组细胞中miR-21的表达,蛋白印迹法检测3组细胞中程序性细胞死亡因子4( PDCD4)蛋白的表达,四甲基偶氮唑蓝(MTT)比色法及流式细胞仪检测3组细胞的增殖及凋亡情况。结果成功构建了表达miR-21的重组干扰载体pSIREN-niR-21质粒,并经酶切鉴定和测序法证实。转染组、阴性对照组和空白对照组OVCAR3细胞中niR-21的表达水平分别为0.26±0.08、1.26±0.21和1.00,转染组明显低于阴性对照组和空白对照组,差异有统计学意义(P＜0.01)。转染组、阴性对照组和空白对照组OVCAR3细胞中PDCD4蛋白的灰度值分别为1443 ±33、858±19和846±16,转染组明显高于阴性对照组和空白对照组,差异有统计学意义(P＜0.01)。转染组、阴性对照组和空白对照组OVCAP3细胞增殖的A值分别为0.661±0.015、0.848±0.150、0.935±0.133,转染组明显低于阴性对照组和空白对照组,差异有统计学意义(P＜0.01)。转染48 h后,转染组细胞的早期凋亡率明显高于阴性对照组和空白对照组[分别为(25.821±0.763)％、(0.010 ±0.003)％、(0.238±0.023)％;P ＜0.01];转染72 h后,转染组细胞的早期凋亡率和晚期凋亡率均明显高于阴性对照组和空白对照组[早期凋亡率分别为( 30.480±0.821)％、(7.792±0.312)％、(7.033±0.257)％,P＜0.01;晚期凋亡率分别为(3.558±0.211)％、(1.557±0.067)％、(1.049±0.028)％,P＜0.05]。结论miR-21参与调节卵巢癌细胞的生长和凋亡过程,可能通过调控PDCD4蛋白的表达而发挥作用。     

Honokiol, a natural therapeutic candidate, induces apoptosis and inhibits angiogenesis of ovarian tumor cells

OBJECTIVES: To observe the anti-tumor activities of honokiol on human ovarian tumor in vitro and in vivo. STUDY DESIGN: Cells were treated with honokiol, and the effects on proliferation and apoptosis were examined by MTT, DNA ladder, Hoechst staining, and flow cytometry assays. Expression of Bcl-2 members and caspase-3 were assessed. Measurements of tumor volume and microvessel densities (MVDs) were performed. RESULTS: Honokiol significantly inhibited proliferation and induced apoptosis, with alteration of Bcl-2 members and caspase-3. Administration of honokiol to tumor-bearing animals decreased MVD and resulted in inhibition of tumor growth. CONCLUSIONS: Honokiol could induce apoptosis and inhibit angiogenesis in vitro and in vivo, suggesting a novel and attractive therapeutic candidate for ovarian tumor treatment.