Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

AIM: To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice.METHODS: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors, and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice. Seventy-five animals were randomized divided into five groups (n = 15). Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg (BF1), 1 mg/kg (BF2) and 0.5 mg/kg (BF3) for d 15-24, respectively. The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15. Ten mice in each group were killed at d 25 and the survival time in each group was calculated. We also observed the morphologic alterations in the myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscopy, measured the apoptotic rate by TUNEL staining method, and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues. RESULTS: The tumor volumes in each group of bufalin were reduced significantly (35.21 ± 12.51 vs 170.39 ± 25.29; 49.83 ± 11.46 vs 170.39 ± 25.29; 83.99 ± 24.63 vs 170.39 ± 25.29, P < 0.01, respectively), and the survival times were prolonged in group BF1-2 (31.8 ± 4.2 vs 23.4 ± 2.1 and 29.4 ± 3.4 vs 23.4 ± 2.1, P < 0.05, respectively), and necrosis was mainly in severe or moderate degree in group BF1-2. No morphologicalchanges were detected in the myocardium, brain, liver and kidney tissues. Apoptotic characteristics could be seen in group BF1-2. The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0%, 10.0%, 20.0%, 10.0% and 20.0%; 90.0%, 80.0%, 80.0%, 40.0% and 30.0%, respectively. Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR. CONCLUSION: Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells. This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax, which may be involved in its anti-tumor mechanism of bufalin.

Anti-tumor effect of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice

Objective: To investigate anti-tumor effect of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. Methods: BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors in nude mice by subcutaneous injection. Then the subcutaneous tumors were implanted into the liver of nude mice, and the orthotopic transplantation tumor models of human hepatocellular carcinoma were established. Seventy-five models were randomized into 5 groups ( n = 15) . Bufalin was injected intraperitoneally into the 3 groups at dose of 1.5,1 and 0.5 mg/kg for day 15 - 24, respectively. NS group were injected equal volume saline as above and adriamycin were injected intraperitoneally into ADM group at dose of 8.0 mg/kg for day 15. Ten mice in each group were killed at day 25 and detected on morphological and ultrastructural changes in myocardium, brain, liver, kidney and tumor tissues by pathology and electron microscope. The survival time in each group were observed. Results: The tumor volumes in each group of bufalin were reduced significantly compared with NS group (P < 0.01), the survival time were prolonged in group Bu 1 and Bu 2 compared with NS group ( P < 0.05), and tumor tissues were mainly necrosis in severe or moderate degree in Bu 1, Bu 2 groups, and mild degree or moderate degree in Bu 3 group. No morphological changes were detected in myocardium, brain, liver and kidney tissues, respectively. Apoptotic characteristics could be seen in tumor tissues of group Bu 1 and group Bu 2. Conclusion: Bufalin has significant anti-tumor effects on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice without marked toxicity. To guide cell apoptosis may be one of its anti-tumor mechanism of bufalin.

Establishment of orthotopic impact/metastasis model of human ovary cancer in nude mice

Objective: To establish a patient-like human ovary carcinoma /spontaneous metastasis model using orthotopic transplanation of histologically intact tumor tissue. Methods: An highly metastatic ovarian tumor line (HO-8910PM: Human serum carcinoma of the ovary )previously grown substaneously was transplanted into the ovicapsule using microsurgery technique .Histologically intact human ovary tumor pieces gained from implantation site were passaged between ovicapsules for four generations. Results: All mice developed ovary tumors and the metastatic rates were about 75%. The tumors only metastasized to liver but no other organs. The earliest appearance of metastasis was 14 d and the average survival period was 20.7±4.89 d.The microscopic appearance of the metastases was similar to the tumor observed in the substaneous xenografts and orthotopically transplanted. Chromosomes analysis exhibited the feature of human carcinoma and retained genetic stability during the processes of passage. Conclusion: Orthotopic implanation provides a suitable micro-enviroment in which ovarian cancer can express its intrinsic clinically-relevant properties. This approach is relevant to the spontaneous development of ovarian cancer and is thought to be a useful model for studies of metastatic mechanism and therapy for ovary cancer.

Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice

AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.

完整瘤组织块原位移植法建立人成骨肉瘤转移模型

目的：建立人成骨肉瘤裸鼠转移模型。方法：采用完整瘤组织块原位移植法获得裸鼠自发性肺转移模型，并对转移模型进行影像学检查、组织学检查及 PCR同源性分析。 结果： 建立裸鼠体内人成骨肉瘤转移模型，其自发性肺转移率达到 100％，肝转移率达 30％。影像学检查及组织学检查均与人成骨肉瘤临床情况相似， PCR同源性分析证实裸鼠肺部转移灶为人成骨肉瘤细胞。结论：裸鼠体内人成骨肉瘤自发性转移模型模拟了临床发病过程，对人成骨肉瘤的治疗、局部肿瘤的生长及转移机制的研究提供了更为理想的模型。

蟾毒灵对裸鼠大肠癌原位移植瘤的抗肿瘤作用及其对凋亡相关基因Bcl-x_L、Bax表达的影响

目的探讨蟾毒灵对裸鼠大肠癌原位移植瘤的抗肿瘤作用及其可能诱导凋亡的机制。方法将60只人结肠癌细胞株HCT-116建立的裸鼠原位移植瘤模型随机分为生理盐水(NS)组、5-Fu组、蟾毒灵低(BL)、中(BM)、高(BH)5组,每组12只,腹腔注射给药持续7d。用药结束后第24天每组分别处死6只裸鼠,完整取出肿瘤,测量肿瘤大小,计算肿瘤抑制率;剩余裸鼠观察带瘤生存期;TUNEL法检测原位移植瘤细胞的凋亡指数;实时荧光定量PCR法和Western blot法检测凋亡相关基因Bcl-xL、Bax mR-NA和蛋白的表达。结果 5-Fu组、BL组、BM组、BH组的肿瘤抑制率分别为69.6%、45.6%、56.2%、58.5%,肿瘤体积与NS组比较明显缩小(P<0.01);BL组、BM组带瘤生存期与NS组相比较明显延长(P<0.05)。TUNEL结果显示蟾毒灵用药组的凋亡指数明显高于NS组(P<0.01);荧光定量PCR和Western结果显示蟾毒灵可抑制Bcl-xL基因表达,促进Bax基因表达(P<0.05)。结论蟾毒灵对裸鼠大肠癌原位移植瘤有显著的抗肿瘤作用,能够抑制Bcl-xL基因和促进Bax基因表达,诱导肿瘤细胞凋亡可能是蟾毒灵抗肿瘤的重要机制之一。

人U87-MG脑胶质瘤细胞裸鼠原位移植模型的建立

目的应用不同数量U87-MG细胞接种裸鼠脑内,建立裸鼠脑胶质瘤模型,观察其生长特性。方法采用立体定向技术,分别将3.0×10^(10)·L^(-1)、4.0×10^(10)·L^(-1)、5.0×10^(10)·L^(-1)浓度的人脑胶质瘤细胞U87-MG单细胞悬液,接种于18只♂裸鼠的右侧尾状核区,每只接种体积为5μL,另取6只裸鼠作为对照,接种同体积Hanks液。观察不同接种量实验鼠的生存状态、成瘤情况及脏器转移灶、带瘤生存期,测量肿瘤的最大径,计算肿瘤体积,将获取的全脑标本制作病理切片,行HE染色和免疫组化检查。结果各接种量的实验组成瘤率均为100%,未见颅外转移病灶,3组裸鼠的平均生存时间分别为(46.50±3.27)d、(38.50±3.28)d、(30.67±3.51)d;病理学检查符合人脑胶质瘤细胞的形态学特征和免疫表型;免疫组化GFAP和S-100蛋白呈阳性表达。结论立体定向脑内定量注射U87-MG细胞制备的人脑胶质瘤裸鼠原位移植模型成瘤率高、颅内生长稳定、颅外远隔部位转移率低,与人脑胶质瘤病理学及形态学特征相似,能为研究胶质瘤的发生、发病机制、生物学特性以及探寻有效的治疗措施提供可靠的动物模型。

蚯蚓纤溶酶抗肝癌转移作用的实验研究

目的探讨蚯蚓纤溶酶(earthworm fibrinolytic enzyme,EFE)对人肝癌细胞转移的影响。方法建立裸鼠人肝癌高转移原位移植瘤模型,造模后7d将裸鼠随机分为模型对照组和EFE高、低剂量组,共3组,每组7只,每天分别给予生理盐水和1600,800uku/kgEFE灌胃,连续30d。实验结束时完整剥除种植瘤并称重;肉眼直接观察种植瘤的肝内播散及腹腔种植情况,计算肝内播散率及腹腔种植率;通过病理切片观察肺转移肿瘤灶的数目;采用RT-PCR及Western blot方法检测移植瘤中FAK(focus adhesion kinase)及β1-整合素蛋白的表达。结果与模型对照组相比,EFE低、高剂量组原位种植瘤瘤重减轻(P<0.05或P<0.01);种植瘤肝内播散率和腹腔种植率降低,其中,EFE高剂量组与模型对照组比较,具有显著性差异(P<0.05);肺转移灶数目明显减少,与模型对照组相比,具有显著性差异(P<0.05或P<0.01)。在原位种植瘤和移植瘤中FAK及β1-整合素在mRNA及蛋白水平的表达方面,EFE高、低剂量组的表达均明显下降,与模型对照组比较具有非常显著性差异(P<0.01)。结论EFE具有抗肝癌转移的作用,其机理可能与EFE能够抑制FAK及β1-整合素的表达有关。

MG-63骨肉瘤原位模型的建立

目的建立裸鼠股骨骨肉瘤原位模型。方法体内连续传代筛选MG-63细胞系获得高成瘤率的细胞,MG-63细胞悬液或MG-63细胞皮下成瘤瘤组织块接种于裸鼠股骨下端。观察MG-63细胞在股骨骨肉瘤原位模型的成瘤特性,并比较两种成瘤方法的成瘤率,常规影像学检查以及肿瘤组织病理检查。结果两周内可见局部肿瘤形成。术后4周X线片可见股骨下段溶骨及成骨改变、肿瘤样骨形成。光镜下可见典型的骨肉瘤病理特征,成骨作用明显。细胞悬液法成瘤率70%,组织块法成瘤率100%,两种方法成瘤率的差异有统计学意义(P<0.05)。结论成功建立了裸鼠股骨下段原位肿瘤移植模型,为骨肉瘤的研究提供了更接近人体内环境的研究基础。

优化胶粘贴法建立裸鼠胃癌原位种植模型

目的通过对两种胶粘贴法建立的胃癌原位种植动物模型的比较研究,为探讨胃癌的发病机制和实验治疗提供理想的动物模型。方法用OB胶和FS生物蛋白胶法分别建立胃癌原位种植动物模型,观察和比较两种方法所建立的模型肿瘤生长状况、转移情况和形态学变化。结果FS生物蛋白胶组未出现肿瘤大片坏死,腹水形成率为85.7%,幽门梗阻发生率为57.1%;而OB胶组肿瘤大片坏死发生率为100%,腹水形成率为14.3%,未出现幽门梗阻。FS生物蛋白胶组有三例出现了肺和脑转移。结论FS生物蛋白胶法建立的裸鼠胃癌原位种植动物模型能更好的模拟人胃癌患者的临床过程,为研究人胃癌转移机制和实验治疗提供理想的动物模型。

建立裸小鼠人胃癌原位移植模型的一种新方法

目的 :建立人胃癌裸小鼠原位移植模型 ,并对不同方法进行比较。 方法 :BAL B/Cnu/ nu裸小鼠 18只 ,随机分为三组 ,胃囊法组通过手术将 SGC- 790 1人胃癌组织块移植到裸小鼠由胃壁粘膜缝制的小囊内 ;缝挂法组以缝挂方法作对比 ;第三组为对照组。待荷瘤鼠濒临死亡时处死进行解剖。 结果 :胃囊法组及缝挂法组原位成瘤率及局部浸润发生率均为 10 0 % ,胃囊法组肝脏转移率为 66.7% ( 4 / 6) ,显著 ( P<0 .0 1)高于缝挂法组 ( 33.3% ) ,而且幽门梗阻及癌性腹水发生率亦明显提高 (分别为 83.33% vs 16.6% ,P<0 .0 0 1;66.7% vs 16.6% ,P<0 .0 0 1)。 结论

应用蛋白质组学技术筛选鉴定锌指蛋白139调控的胃癌转移相关蛋白质

目的以胃癌SGC7901细胞原位移裸鼠模型为对象,通过荧光双向差异凝胶电泳(2D-DIGE)结合液质联用(LC-MS)质谱分析技术鉴定ZNF139调控的胃癌转移相关蛋白质。方法合成针对ZNF139的小干扰RNA(ZNF139-si RNA),以ZNF139-si RNA转染人胃癌细胞株SGC7901,G418筛选。以ZNF139-si RNA质粒转染的胃癌细胞、阴性质粒转染的胃癌细胞及普通胃癌细胞分别进行裸鼠胃癌原位移植。造模成功后取出原位移植瘤及腹腔转移淋巴结。荧光双向差异凝胶电泳(2D-DIGE)技术分别分离ZNF139-si RNA各组原位移植瘤及腹腔转移淋巴结蛋白质;选定差异点,胶内酶解后,液质联用(LC-MS)质谱分析技术鉴定蛋白质。蛋白印迹(Western blot)技术验证差异蛋白质的表达。结果转染ZNF139-si RNA质粒后SGC7901细胞中ZNF139的表达受到有效抑制。与阴性质粒组及空白组比较,阳性质粒组原位移植瘤生长更慢(P<0.05),且腹腔淋巴结转移率更低(P<0.05)。蛋白质组学结果发现在阳性质粒组原发灶中Fascin、hn RNPA2/B1表达下调,ANXA1表达上调;阳性质粒组转移淋巴结中ANXA5表达下调(P<0.05)。Western blot验证结果与蛋白质组学结果相符。结论 ZNF139可能通过调节Fascin、hn RNPA2/B1、ANXA1、ANXA5促进胃癌淋巴结转移。

人CHG-5胶质瘤细胞裸鼠原位移植模型的建立及其生物学特性分析

目的 建立人脑胶质瘤裸鼠脑内原位移植动物模型并探讨其生物学特性。方法 采用瘤细胞悬液接种法 ,将人脑CHG 5胶质瘤细胞接种于裸鼠大脑实质内。分别于接种后 8、14、19、2 4和 3 0d处死动物并行病理检查、胶质纤维酸性蛋白免疫组化、染色体核型分析及透射电镜检查。结果 肿瘤移植成瘤率为 10 0 % ,肿瘤生长稳定 ,肿瘤病理学检查符合人脑胶质瘤细胞的形态学特征和免疫表型。结论 本移植瘤模型能作为研究胶质瘤发生、生物学特性以及治疗研究的可靠动物模型。接种后

人甲状腺未分化癌细胞系TA-K裸鼠原位移植模型的建立

目的 建立人甲状腺未分化癌裸鼠自发转移模型 ,观察移植后肿瘤生长情况和转移规律。方法 用微量注射器于裸小鼠甲状腺侧叶内 (甲状腺原位移植组 )和皮下 (皮下对照组 )注入等体积不同浓度的人甲状腺未分化癌细胞系TA K细胞悬液 ,观察动物体重、一般状态、颈部情况及记录生存时间 ,并动态观察肿瘤局部生长和转移情况 ;取甲状腺、气管、食管、颈部及纵膈淋巴结、肺和骨组织行病理组织学检查 ,并取移植瘤组织常规进行染色体分析。结果 甲状腺原位移植组于注射人甲状腺未分化癌细胞系TA K细胞悬液后 2 4～ 3 4d裸鼠先后出现呼吸困难 ,实验侧甲状腺肿物呈膨胀性生长 ,侵及颈前肌及周围组织 ,压迫气管造成呼吸困难。病理组织学检查证实原位移植成瘤率为 10 0 % ,颈部淋巴结转移率为 5 /10 ,肺转移发生率为 3 /10 ,骨转移发生率为 1/10。移植瘤组织染色体分析证实为人类肿瘤。皮下移植组见移植瘤有完整包膜 ,未见侵犯局部肌层 ,也无局部和淋巴结转移。结论 利用裸鼠甲状腺原位TA K细胞微量注射法 ,可以成功建立人甲状腺未分化癌裸鼠原位移植模型 ,该模型是较为理想的用于研究甲状腺癌转移的动物模型。

3种方法构建BALB/c裸鼠BEL-7402人肝癌模型

【目的】以3种不同方法构建BALB/c裸鼠BEL-7402人肝癌模型,并观察BALB/c裸鼠肿瘤生长情况。【方法】将51只BALB/c裸鼠分为A、B、C 3组,每组17只。A组动物皮下注射0.2 m L BEL-7402人肝癌细胞,B组动物于肝脏原位注射0.05 mL BEL-7402人肝癌细胞与Matrigel Matrix的混合物,C组动物于肝脏原位接种BEL-7402人肝癌细胞瘤块组织。从接种后第2周至第5周,每周测定裸鼠体质量,且每组随机取3只动物解剖取肿瘤测量其大小和质量。第5周后,观察记录各组剩余动物(每组5只)的一般状态和存活天数。采用苏木素—伊红(HE)染色观察肿瘤组织病理学变化。【结果】A、B、C 3组实验动物成瘤率均为100%。5周后,A、B、C 3组剩余动物存活天数分别为(90.8±10.2)、(75.6±14.0)、(67.4±11.1) d。解剖所取肿瘤呈结节状,组织病理学检查可见肿瘤细胞呈一定方向排列,细胞呈梭形、多边形,异型明显,可见核分裂。【结论】本实验所采用的3种不同方法均能成功建立BALB/c裸鼠BEL-7402人肝癌模型。

裸小鼠胃癌原位移植模型的建立

目的建立一种新的裸小鼠胃癌原位移植模型。方法采用Matrx VIP 3000型气体麻醉系统对实验动物进行麻醉。分别用"包埋法"、"挂线法"、和"胃囊法"建立BALB/c裸小鼠胃癌原位移植瘤模型。术后用Caliper IVIS Kinetic小动物活体成像系统对实体瘤的生长情况进行检测和分析。术后28 d对肿瘤组织进行组织病理学检查。结果采用包埋法建立胃癌原位移植裸小鼠模型,除了与其它常用方法一样具有高移植成功率以外,还具有操作简便、时间短、难度低、肿瘤组织不易与其它组织直接接触等特点。结论包埋法能快速制备大批量小鼠胃癌原位移植模型,为胃癌原位移植模型相关研究提供便利。

人胃癌裸鼠胃原位种植转移模型的建立和改进

目的:建立人胃癌裸鼠胃原位种植转移模型。方法:用人胃癌细胞SGC-7901悬液接种于裸鼠皮下,形成稳定传代的皮下移植瘤。将皮下移植瘤组织再接种于裸鼠胃浆肌层,观察移植肿瘤的生长状况、移植成功率和自发转移的发生率及组织学变化等生物学特性。结果:肿瘤组织块保留了人胃腺癌的组织学特点,人胃癌裸鼠原位移植模型成瘤率为100%(20/20),肝脏转移率为45%(9/20)。结论:人胃癌裸鼠原位移植瘤模型的生物学行学与人胃癌自然生长和转移过程相似,为研究人胃癌转移机制提供了理想的模型。

建立裸小鼠人胃癌原位移植模型的一种新方法

建立人胃癌裸小鼠原位移植模型，并对不同方法进行比较。方法：BALB／Cnu／un裸小鼠18只，随机分为三组，胃囊法组通过手术将SGC－7901人胃癌组织块移植到裸小鼠胃壁缝制的粘膜小囊内；缝挂法组以缝挂方法作对比；第三组为对照组。待荷瘤鼠濒临死亡时处死进行解剖检查。结果：胃囊法组及缝挂法组原位成瘤率及局部浸润发生率均为100％，胃囊法组肝脏转移率为66．7％（4／6），显著P＜0．01高于挂法组（33．3％），且幽门梗阻及癌性腹水发生率亦明显提高（分别为83．33％vs16．6％P＜0．01；66．7％vs16．6％，P＜0.001）。结论：胃囊法建立的模型能更好地再现人胃癌的生长特性。

蟾毒灵对裸鼠结肠癌原位移植瘤凋亡基因Caspase-3表达的影响

目的:探讨蟾毒灵治疗裸鼠结肠癌原位移植瘤的作用及机制。方法 :应用不同剂量蟾毒灵(0.5、1.0、1.5 mg/kg)处理人结肠癌细胞株HCT-116建立的裸鼠原位移植瘤模型,分别用生理盐水(NS)(0.2 mL/只)、5-FU(25 mg/kg)做阴性(NS组)和阳性对照(5-FU组),测量移植瘤的体积,观察蟾毒灵对移植瘤的肿瘤抑制率、裸鼠生存期的影响;HE染色观察移植瘤的坏死程度;TUNEL标记法检测肿瘤细胞的凋亡指数;荧光定量PCR方法检测基因Caspase-3 mRNA的表达,免疫组化法和Western印迹法检测Caspase-3蛋白的表达。结果:蟾毒灵各剂量组和5-FU组裸鼠原位移植瘤体积明显小于NS组(P<0.05);NS组,5-FU组和蟾毒灵0.5、1.0、1.5 mg/kg剂量组的裸鼠中位生存期分别为40、37和47、46、45 d,生存分析显示蟾毒灵各剂量组裸鼠的生存时间与NS组相比明显延长;1.0和1.5 mg/kg剂量组和5-FU组移植瘤的坏死程度增加(P<0.05);蟾毒灵各组移植瘤的凋亡指数与NS组相比明显增加(P<0.05),凋亡相关基因Caspase-3 mRNA和蛋白表达明显升高(P<0.05)。结论:蟾毒灵能够抑制裸鼠人结肠癌原位移植瘤的生长,促进肿瘤细胞凋亡,其机制可能与上调基因Caspase-3表达有关。

裸鼠原位肝癌动态影像检查与病理对照研究

目的影像学动态监测裸鼠原位肝癌建模后肿瘤生长并与病理对照,判断干预治疗的合适时期。方法 HepG2细胞注射裸鼠皮下,成瘤后切成1 mm^3组织块,植入15只裸鼠肝内。建模后第4、6、8周分别对5只裸鼠进行超声、磁共振成像(magnetic resonance imaging,MRI)检查,测量肿瘤长径,完毕麻醉处死裸鼠,解剖观察肝成瘤状况,测量肿瘤长径,标本送病理。结果裸鼠肝癌成瘤率80%,肿瘤均为单个,边界清晰。超声检出率75%,MRI检出率100%。4周时肿瘤平均长径4 mm,6周时平均长径7 mm,8周时平均长径11 mm。Wilcoxon秩和检验,超声与解剖比较,P=0.0059,MRI与解剖比较,P=0.208。4、6周时监测,肝癌超声表现均匀低回声;T2WI表现为边界清晰、均匀一致高信号;病理表现瘤细胞致密、核大、异型性明显。8周时监测,超声表现为不均匀低回声;T2WI为形态不规则高信号,中心杂乱、分布不均;病理表现为肿瘤内部坏死。结论组织块建模裸鼠原位肝癌成瘤率高。影像学特征与病理表现相关。MRI是全程监测肿瘤生长的有效影像学方法。1 mm^3瘤块接种裸鼠肝,4～6周可能是进行干预治疗的最佳时期。