The Inhibitory Effect of Endostatin and Doxycycline Administration on B16 Melanoma Angiogenesis and Cellular Proliferation

OBJECTIVE To investigate the effect of endostatin and doxycycline on melanoma cellular proliferation and tumor angiogenesis.METHODS The effects of endostatin and doxycycline were studied in mice transplanted with B16 melanoma cells.The mice were divided into 4 groups that were treated as follows:endostatin treatment(E group),doxycycline treatment(D group),endostatin plus doxycycline trearment(DE group),controls(C group) received no treatment.Following 9 days of treatment the tumor tissue was removed to compare the differences in the tumor necrotic rate and micro-vessel density(MVD) among the different groups.Immunohistochemical staining was conducted to detect the expression of proliferating cell nuclear antigen(PCNA)in the di?erent groups. RESULTS The MVD of the 3 experimental groups was significantly less than the control group,(F=10.888,P<0.05),indicating that doxycycline and endostatin can inhibit tumor angiogenesis by decreasing the tumor blood supply.This effect results in inhibition of tumor cellular proliferation and promotion of tumor cell necrosis.The tumor cell necrotic rate of the 3 experimental groups were all significantly higher than the C group(F=7.229,P<0.05) and the difference between the DE and C groups also was statistically significant.PCNA expression in all 3 experimental groups was statistically less than the C group(F=17.729,P<0.05). CONCLUSION The combined use of endostatin and doxycycline in vivo can influence PCNA expression and angiogenesis in melanoma,and significantly inhibit melanoma cellular proliferation.     

靶向IGFIR的siRNA抑制人肝癌细胞SMMC7721裸鼠移植瘤的实验研究

Objective:To investigate the effect of insulin-like growth factor 1 receptor (IGF1R) small interfering RNA (siRNA)on the growth of human liver cancer SMMC7721 cell xenograft in nude mice.Methods:siRNAtargeting IGF1R was designed,and plasrnid SMMC7721-1GF1R-siRNA was constructed and transfected into SMMC7721 cells (SMMC7721-1GF1R-siRNAcells); the cells transfected with SMMC7721-1GF1 R-mutation (SMMC7721-1GF1 R-mutation cells) were used as negative control,and untransfected cells as empty control.Stable cell clones were screened by G418,and transplanted into nude mice to establish cancer xenograft.Tumor growth was monitored.Tumor morphology was observed with HE staining.The expression of IGF1R protein in tumor tissues was detected by Western blot.Microvessel density (MVD) in tumor tissues was detected by SP immunohistochemistry.Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay.Results:The tumor volume was significantly smaller in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (P＜0.05).Necrosis and cell apoptosis were found in SMMC7721-1GF1R-siRNA group.The expression of tGF1R protein was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (P＜0.05).MVD was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups (11.3±4.4 vs.36.7±7.6 and 28.4±6.5,P＜0.05).The apoptosis rate of tumor cells was significantly higher in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1 R-mutation and SMMC7721 groups [(50.2±6.4)% vs.(5.4±1.0)% or (6.0±2.1)%,P＜0.05].Conclusion:1GF1R siRNA can inhibit the growth of SMMC7721 cell xenograft in nude mice.     

重组人生长激素联合氟尿嘧啶对人胃癌裸小鼠皮下移植瘤作用的实验研究

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neoplasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stomach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P＜0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P＜0.05), but it was no significant difference between rhGH/5-FU groups and control group (P＞0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P＞0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P＜0.05). They were no significant difference between rhGH/5-FU groups and 5-FU group (P＞0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index(PI) were not significantly changed in rhGH groups compared with control group (P＞0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P＞0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.     

Experimental Studies of the Therapeutic Effect of Gypsophila Oldhamiana Gypsogenin on Lewis Lung Cancer in Mice

OBJECTIVE To observe the inhibitory effect of Gypsophila oldhamiana gypsogenin (GOG) on Lewis lung cancer growth,and to investigate the mechanism of its anti-tumor effect. METHODS A mouse model bearing Lewis lung cancer was used.The 5 experimental groups were divided into a positive control (cis-diaminedichloroplatinum),a negative control,and high,medium and low-GOG dosage groups.The inhibitory action of GOG administration on the lung cancer was observed.After GOG treatment,the lungs were taken out and a lung coefficient computed.The expressions of VEGF,Bcl-2,Bax and P53 in the cancers were determined using immunohistochemical staining. RESULTS The tumor weight of the mice given various doses of GOG was significantly lower compared to the negative-control group (P<0.01),and the lung coefficient of the groups given high and low GOG doses was significantly lower compared to the negative-control group (P<0.01).Immunohistochemical results were shown as follows:i) The VEGF and Bcl-2 expressions in the GOG groups were significantly lower than that of the negative-control group (P<0.05);ii) Bax expression in the groups treated with high and medium GOG doses was significantly higher compared to the negative-control group (P<0.05);iii) The mutant P53 expression in the GOG-treated groups was significantly lower compared to the negative-control group (P<0.05).CONCLUSION GOG can inhibit the growth and metastasis of Lewis lung cancer,and may exert its mechanism of tumor control by inhibition of tumor angiogenesis and induction of apoptosis.     

Effect of 125I seed brachytherapy and radiotherapy on the growth of transplanted human lung cancer cell line A549 in nude mice and the impact of HIF-1α expression after therapy

Objective To study the inhibitory effects of radiotherapy and 125I seed brachytherapy on the growth of transplanted human lung cancer cell line A549 in nude mice and the impact of HIF-1αexpression after therapy.Methods Forty nude mice bearing human lung cancer cell line A549 were randomly divided into control group,radiotherapy group,125I seed brachytherapy group and radiotherapy + 125I seed group when tumor volume achieved (300±50) mm3.The tumor growth was observed and the alteration of tumor size was calculated at different time.On 15th day,the expression of HIF-1α was detected by immunohistochemistry and western blot.Results When eighth day after treatment,compared with the control group,the tumor volume of the combined treatment group was significantly smaller (t = 46.4,P ＜0.05).After fifteenth day after treatment,compared with control group,the group of radiotherapy,125I seed brachytherapy and radiotherapy + 125I seed gained the tumor control rate of 45.9 %,44.4 %,69.4 % respectively.Compared with other groups,the change of expression of HIF-1α in the combined treatment group was not significant (P ＞0.05).Conclusion Radiotherapy combined with 125I seed brachytherapy can inhibit the growth of transplanted human lung cancer cell line A549 in nude mice,and the tumor regression can be observed in early stage.But in our study,the expression of HIF-1α in tumors cannot be inhibited by 125I seed.     

Effect of Neoadjuvant CAF Regimen on the Expression of BCSG1 in Breast Cancer

Objective： To evaluate the efficacy of neoadjuvant chemotherapy and explore a sensitive and objective way in the evaluation of neoadjuvant chemotherapy, the pathological changes and BCSG1 expression were studied by pathological and immunohistochemical method in breast cancer patients with CAF neoadjuvant chemotherapy （Cyclophosphamide, Adriamycin and Fluorouracil, CAF） and those without at the same period. Methods： Specimens were obtained from 34 breast cancer patients receiving neoadjuvant CAF regimen chemotherapy （CAF group） and 110 breast cancer patients not receiving neoadjuvant chemotherapy （control group）. The BCSG1 expression was detected by SP immunohistochemistry. Correlation between BCSG1 expression and pathological response to CAF neoadjuvant chemotherapy was analyzed. Results： Overall response rate to neoadjuvant chemotherapy was 79.4%. The strong cytoplasm expression of BCSG1 was significantly lower in CAF group than in control group （29.4% vs. 64.5%, P〈0.01）. In CAF group, the positive cytoplasm expression in partial response （PR） （grade Ⅱ） cases was significantly lower than that in no response （NR） （grade Ⅲ） cases （P=0.002）. Conclusion： Neoadjuvant chemotherapy of CAF regimen could decrease the nuclear expression of BSCG1 in breast cancer.     

Effect of 125I seed brachytherapy and radiotherapy on the growth of transplanted human lung cancer cell line A549 in nude mice and the impact of HIF-1α expression after therapy

Objective To study the inhibitory effects of radiotherapy and 125I seed brachytherapy on the growth of transplanted human lung cancer cell line A549 in nude mice and the impact of HIF-1αexpression after therapy.Methods Forty nude mice bearing human lung cancer cell line A549 were randomly divided into control group,radiotherapy group,125I seed brachytherapy group and radiotherapy + 125I seed group when tumor volume achieved (300±50) mm3.The tumor growth was observed and the alteration of tumor size was calculated at different time.On 15th day,the expression of HIF-1α was detected by immunohistochemistry and western blot.Results When eighth day after treatment,compared with the control group,the tumor volume of the combined treatment group was significantly smaller (t = 46.4,P ＜0.05).After fifteenth day after treatment,compared with control group,the group of radiotherapy,125I seed brachytherapy and radiotherapy + 125I seed gained the tumor control rate of 45.9 %,44.4 %,69.4 % respectively.Compared with other groups,the change of expression of HIF-1α in the combined treatment group was not significant (P ＞0.05).Conclusion Radiotherapy combined with 125I seed brachytherapy can inhibit the growth of transplanted human lung cancer cell line A549 in nude mice,and the tumor regression can be observed in early stage.But in our study,the expression of HIF-1α in tumors cannot be inhibited by 125I seed.     

Antitumor effects of artesunate on human breast carcinoma MCF-7 cells and IGF-IR expression in nude mice xenografts

Purpose： The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate （ART） action on breast cancer in vivo using tumor transplanted nude mice. Methods： The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART alone or in combination with cyclophosphamide （CTX） or normal saline （NS）. The tumor inhibitory effects were observed and compared, and the ultrastructural morphology of the transplanted tumor cells was observed by electron microscopy. The apoptosis rates and cell cycle status were detected by flow cytometry （FCM）. The expression of apoptosis-related proteins p53, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry and IGF-IR was detected by western blot. The expression correlation for these proteins was also analyzed. Results： The tumor inhibition rates in the low dose ART group, high dose ART group, CTX group and combined drug therapy group were （24.39±10.20）%, （40.24±7.02）%, （57.01±5.84）% and （68.29±5.1）%, respectively. The cell cycle was arrested in phase G0/Gt after treatment with ART. The expression of Bcl-2 was significantly reduced, and the expression levels of Bax and Caspase-3 were significantly increased in the ART group compared to the negative control saline group. There was no significant difference detected in p53 expression. The Bcl-2 level was negatively related to Bax and Caspase-3. The western blotting results showed IGF-IR downregulation. Conclusions： ART inhibits the growth of MCF-7 breast tumor cell xenografts in nude mice. The anti-tumor mechanism of ART for human breast carcinoma in nude mice might be correlated with the alteration of apoptosis related protein expression, which may further induce apoptosis and inhibit cell proliferation.     

INHIBITORY EFFECT OF DEMO ON THE GROWTH OF TRANSPLANTED HUMAN COLON CANCER IN NUDE MICE

A human colon cancer cell line Hce- 8693 was heterotransplanted in nude mice. Polyamine blosythesis Inhibitor a- dlfiuoromethylomithine (DFMO ) show a marked reproducible inhibition in this model. The size and weight of transplanted tumor In DFMO group were smaller than those of the control group and the average inhibition rate was 72.8% (P < 0.001) . DFMO showed higher tumor inhibitory rate than 5-Fu (35. 4%) (P<0. 001) . Furthermore. DFMO demonstrated less severe bone marrow inhibition in the nude mice than 5-Fu (20. 0% Vs 53. 2%. P<0. 001) .There was no synergistic action in these two drugs at the experimental dose. The concentration of putrescine and spermidine in the plasma and tumor tissue in the DFMO group were 70% lower than those of the control group (P<0. 001) . These results indicate that the anti-tumor effect of DFMO might be explained by the inhibition of polyamine biosynthesis and this study provides an experimental basis for future clinical application of DFMO.     

不同化疗方案对裸鼠MCF-7乳腺癌移植瘤PCNA和Bcl-2表达的影响

目的：研究不同化疗方案对乳腺癌组织PCNA和Bcl-2的影响,探讨二者与化疗的关系及评价疗效的价值。方法：制备MCF-7乳腺癌荷瘤裸鼠模型,化疗后观察移植瘤病理组织学疗效,用免疫组化SP法显示乳腺癌组织PCNA和Bcl-2表达情况。结果：（1）各化疗组瘤组织PCNA表达显著低于对照组（P〈0．05）,且NP、TP和Xeloda组显著低于CMF、CAF组（P〈0．05）。PCNA表达与病理疗效显著相关（P=0．001）。（2）CAF、NP、TP和Xeloda化疗组Bcl-2蛋白表达显著高于对照组（P〈0．05）,且TP组显著高于CMF、CAF组（P〈0．05）。Bcl-2表达与病理疗效无显著相关性（P=0．093）。结论：化疗可降低乳腺癌组织PCNA表达,并增强Bcl-2的表达,且不同化疗方案对二者影响的差异有显著性。PCNA可作为评价乳腺癌化疗效果的参考指标,对选择化疗方案可能有指导意义。     

生酮饮食对人肺癌细胞裸鼠皮下移植瘤生长的影响

目的： 建立人肺癌细胞裸鼠皮下移植瘤模型,观察生酮饮食对裸鼠皮下移植瘤生长的影响并对其作用机制进行研究。方法： 10只雌性BALB/c裸鼠右下肢皮下注射人肺癌A549细胞,建立肺癌细胞裸鼠移植瘤模型后,随机分为标准饮食组（SD组）和生酮饮食组（KD组）,分组当天测量裸鼠体质量、移植瘤体积、血糖及血酮浓度,以后每5 d测量1次。接种肿瘤细胞后第30天,摘眼球取血处死裸鼠,取血后进行血脂四项检测。剥离移植瘤组织,分别采用Western blot及免疫组织化学方法检测裸鼠移植瘤组织中4-HNE蛋白的表达水平。结果： 接种肿瘤细胞后第15天起,KD组裸鼠血酮浓度较SD组升高,血糖浓度较SD组降低,差异均有统计学意义（P < 0.05）。接种肿瘤细胞后第20天起,KD组裸鼠体质量及移植瘤体积小于SD组,差异均有统计学意义（P < 0.05）。接种肿瘤细胞后第30天,KD组裸鼠的总胆固醇（CHOL）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）浓度高于SD组,甘油三酯（TG）浓度低于SD组,差异均有统计学意义（P < 0.05）。Western blot法分析结果显示KD组裸鼠移植瘤组织中4-HNE蛋白相对表达水平（1.45±0.10）高于SD组（1.00±0.03）,差异有统计学意义（P < 0.05）。免疫组化法检测结果显示KD组裸鼠移植瘤组织中4-HNE表达水平（4.40±0.89）高于SD组（2.40±0.89）,差异有统计学意义（P < 0.05）。结论： 生酮饮食可以抑制人肺癌细胞裸鼠皮下移植瘤的生长,其作用机制可能与肿瘤细胞氧化应激的增强有关。     

生酮饮食对人肺癌细胞裸鼠皮下移植瘤生长的影响

目的： 建立人肺癌细胞裸鼠皮下移植瘤模型，观察生酮饮食对裸鼠皮下移植瘤生长的影响并对其作用机制进行研究。方法： 10只雌性BALB/c裸鼠右下肢皮下注射人肺癌A549细胞，建立肺癌细胞裸鼠移植瘤模型后，随机分为标准饮食组（SD组）和生酮饮食组（KD组），分组当天测量裸鼠体质量、移植瘤体积、血糖及血酮浓度，以后每5 d测量1次。接种肿瘤细胞后第30天，摘眼球取血处死裸鼠，取血后进行血脂四项检测。剥离移植瘤组织，分别采用Western blot及免疫组织化学方法检测裸鼠移植瘤组织中4-HNE蛋白的表达水平。结果： 接种肿瘤细胞后第15天起，KD组裸鼠血酮浓度较SD组升高，血糖浓度较SD组降低，差异均有统计学意义（P < 0.05）。接种肿瘤细胞后第20天起，KD组裸鼠体质量及移植瘤体积小于SD组，差异均有统计学意义（P < 0.05）。接种肿瘤细胞后第30天，KD组裸鼠的总胆固醇（CHOL）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）浓度高于SD组，甘油三酯（TG）浓度低于SD组，差异均有统计学意义（P < 0.05）。Western blot法分析结果显示KD组裸鼠移植瘤组织中4-HNE蛋白相对表达水平（1.45±0.10）高于SD组（1.00±0.03），差异有统计学意义（P < 0.05）。免疫组化法检测结果显示KD组裸鼠移植瘤组织中4-HNE表达水平（4.40±0.89）高于SD组（2.40±0.89），差异有统计学意义（P < 0.05）。结论： 生酮饮食可以抑制人肺癌细胞裸鼠皮下移植瘤的生长，其作用机制可能与肿瘤细胞氧化应激的增强有关。     

增殖诱导配体小干扰RNA对人结直肠癌裸鼠移植瘤细胞增殖和凋亡的影响

目的 研究增殖诱导配体(APRIL)小干扰RNA(siRNA)对人结直肠癌裸鼠移植瘤细胞增殖和凋亡的抑制作用.方法 建立人结直肠癌裸鼠移植瘤模型,将裸鼠分为3组,瘤块内分别注射APRIL siRNA、空载体和PBS液,每2天注射1次,共2周.采用实时荧光定量PCR法和免疫组化SP法检测APRIL siRNA对APRILmRNA和蛋白表达的影响,采用酶联免疫吸附(ELISA)法检测肿瘤内增殖细胞核抗原(PCNA)含量的变化,采用免疫组化SP法检测肿瘤内bcl-2和bcl-xl蛋白的表达,采用原位末端标记(TUNEL)法检测肿瘤细胞的凋亡.结果 APRIL siRNA能敲低APRIL基因的表达水平,APRIL siRNA组移植瘤内APRIL mRNA的相对表达量为(0.13 ±0.05)×10-3,明显低于空载体组[(0.95 ±0.04)× 10-3]和空白对照组[(0.96±0.05)×10-3,P＜0.05].APRIL siRNA组APRIL蛋白的表达比空载体组和空白对照组降低了(87.5%±5.0%,P＜0.05).APRILsiRNA组裸鼠移植瘤生长缓慢,瘤块重量较空载体组和PBS对照组明显降低(P＜0.05).APRIL siRNA组移植瘤内PCNA的含量为(176.8±18.1)ng/ml,明显低于空载体组[(330.0±20.5)ng/ml]和空白对照组[(328.4±22.8)ng/ml,P＜0.05];bcl-2和bcl-xl蛋白的表达量也较空载体组和空白对照组明显降低(P＜0.05).APRIL siRNA组移植瘤内凋亡细胞的数量增多,凋亡率为40.1%±2.5%,明显高于空载体组(2.5%±0.1%)和空白对照组(2.5%±0.2%,P＜0.05).结论 APRIL siRNA能在裸鼠体内抑制人结直肠癌细胞的增殖,并促进细胞凋亡,达到显著的抑瘤效果.APRIL基因可能成为人结直肠癌基因靶向沉默治疗的重要候选基因之一.     

重组肿瘤抑素血管生成抑制相关肽对裸鼠移植性卵巢癌的抑制作用

目的 观察肿瘤抑素改造后所得血管生成抑制相关肽(21肽)的抗血管生成活性及对裸鼠移植卵巢癌的抑制作用.方法 用亲和层析法纯化21肽.观察接种SKOV3细胞系的裸鼠经21肽治疗后的肿瘤生长情况,检测21肽对肿瘤组织的微血管密度和免疫组织化学指标的影响.结果 经21 d的治疗后,21肽组平均抑瘤率可达53.17%.21肽组肿瘤组织微血管密度(CD34表达)为6.324±1.643,与对照组(16.127±2.535)比较明显降低(P＜0.05).21肽组肿瘤组织的增殖细胞核抗原(PCNA)、血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP-2)呈低表达(P＜0.01),而基质金属蛋白酶抑制因子2(TIMP-2)呈高表达(P＜0.01).结论 21肽具有显著的抗血管生成活性,对卵巢癌具有较好的抑制作用,其抑制卵巢癌的作用机制可能与其降低新生血管形成和调解血管生成相关因子的表达有关.     

鼻咽癌移植瘤cyclin D1表达与化疗相关性

[目的]通过比较化疗前后裸小鼠CNE-2鼻咽癌移植瘤cyclin D1蛋白表达的变化．评价化疗对cyclin D1蛋白表达的影响。[方法]将荷瘤小鼠随机分成3组：5-Fu组、DDP组和对照组，取肿瘤组织活检后开始化疗。化疗后测体重及肿瘤大小。一周后再次活检。用Western Blot方法检测活检组织cvclin D1蛋白表达。[结果]两化疗组化疗后肿瘤生长抑制明显，与对照组比较差异显著。随着时间的延长和肿瘤体积的逐渐增大，3组cyclin D1表达均逐渐增强，但两化疗组与对照组比较差异无显著性（P〉0．05）。3组中cyclin D1高、低表达者化疗后肿瘤体积均无显著差异（P〉0．05）。[结论]鼻咽癌组织cyclin D1表达高、低不能预测化疗的敏感性：表达程度在化疗前后是稳定的。     

Antitumor and vascular effects of apatinib combined with chemotherapy in mice with non-small-cell lung cancer

Objective The aim of this study was to investigate the antitumor and vascular effects of apatinib use combined with chemotherapy on mice with non-small-cell lung cancer (NSCLC). Methods First, 60 tumor-bearing nude mice were randomly divided into control, low-dose, and high-dose groups. Four nude mice per group were sacrificed before administration and on days 1, 3, 7, and 10 after administration. HIF-1α expression in tumor tissues was detected. Second, 32 nude mice were randomly divided into control, premetrexed, synchronous, and sequential groups. The weights and tumor volumes of mice were recorded. Results (1) HIF-1α expression decreased significantly on days 3 and 7 after low-dose apatinib treatment. There was no significant difference in HIF-1α expression in the high-dose apatinib group (P > 0.05). MMP-2 and MMP-9 expression levels in the low-dose apatinib group were significantly lower than those in the control group (P < 0.05). (2) In the low-dose apatinib group, the microvessel density increased gradually from days 3 to 7 post-treatment, while that in the high-dose apatinib group decreased significantly. (3) The inhibitory effect of sequential therapy using low-dose apatinib and pemetrexed was optimal, while that of synchronous treatment was not better than that of pemetrexed usage alone. Sequential treatment using low-dose apatinib and pemetrexed exerted the best antitumor effect. (4) The expression levels of p-AKT, p-mTOR, p-MEK, and p-ERK in the sequential group were significantly lower than those in the other three groups (P < 0.05). Conclusion Apatinib usage involves certain considerations, such as dose requirements and time window for vascular normalization during lung cancer treatment in nude mice, suggesting that dynamic contrast-enhanced magnetic resonance imaging and other tests can be conducted to determine the vascular normalization window in patients with lung cancer and to achieve the optimal anti-vascular effect.     

雷替曲塞对人胃癌裸鼠移植瘤生长的影响及其机制

  目的   初步探索雷替曲塞对人胃癌裸鼠皮下移植瘤生长的影响及其机制。   方法   1）建立人胃癌细胞MGC-803裸鼠皮下移植瘤模型；2）药物干预后观察荷瘤鼠一般情况、体重、瘤重并计算抑瘤率；3）流式细胞仪测定瘤细胞的周期分布和凋亡；4）采用RT-PCR、Western blot印迹法检测各组肿瘤p53 mRNA及p53蛋白的表达水平。   结果   经雷替曲塞及5-Fu作用后，与对照组相比，两组裸鼠的体重明显下降，瘤体积缩小，抑瘤率分别达到49.02%和45.75%。雷替曲塞组和5-Fu组瘤细胞的G₀/G₁期比例较对照组比例明显降低（P < 0.01），而S期比例较对照组明显升高（P < 0.01）。雷替曲塞组和5-Fu组裸鼠肿瘤p53 mRNA与蛋白表达水平均显著升高（P < 0.01），但雷替曲塞组和5-Fu组之间并无差异。   结论   1）雷替曲塞对人胃癌细胞MGC-803裸鼠移植瘤生长有抑制作用，且与5-Fu抑瘤效果相似；2）雷替曲塞可以诱导人胃癌细胞MGC-803裸鼠移植瘤细胞周期S期的阻滞，并诱导移植瘤细胞凋亡；3）雷替曲塞可通过上调p53 mRNA和蛋白的表达水平来发挥抑瘤作用。       

Preliminary investigation of the inhibitory effects of the tyroservaltide (YSV) tripeptide on human hepatocarcinoma BEL-7402

This study aimed to investigate the inhibitory effect of tyroservaltide (YSV) on the human hepatocarcinoma BEL-7402 transplanted into nude mice and to explore its possible anti-tumor mechanism. Nude mice bearing xenografts of the human BEL-7402 hepatoma were given daily i.p. injections of YSV or saline (as a control) after the tumor were transplanted. Calculating tumor volume and measuring tumor weight determined the extent of inhibition of xenografts. The ultrastructure of tumor cells was observed by electron microscopy. Proliferating cell nuclear antigen (PCNA) expression in tissues of the YSV-treated group was observed by immunohistochemistry. Apoptosis of tumor tissue cells was assayed by the terminal transferase uridyl nick end labeling (TUNEL) method. At doses of 80 microg/kg/d and 160 microg/kg/d, YSV could significantly inhibit growth of tumors transplanted into nude mice, with inhibition rates of 60% and 64%, respectively, compared with that of the controls (P < 0.05). Moreover, YSV changed the ultrastructure of tumor cells, resulting in necrosis and apoptosis of the tumor cells. Compared with the saline group, the expression of PCNA in tumor tissue decreased and the count of apoptotic cell increased. Therefore, YSV can significantly inhibit the growth of human hepatocarcinoma BEL-7402 in nude mice, decrease the expression of PCNA in tumor tissue, and induce tumor cell apoptosis.     

microRNA-486对结直肠癌裸鼠皮下移植瘤生长抑制作用及其机制的研究

背景与目的：越来越多的证据表明microRNA在生物进程的各个阶段发挥重要作用。在不同的恶性肿瘤中microRNA-486表达上调或者下调,但microRNA-486对人结直肠癌潜在的作用尚不清楚。该研究旨在探讨其对细胞系SW620裸鼠皮下移植瘤生长情况的影响及其可能的作用机制。方法：取18只裸鼠,按简单随机法分为实验组、阴性对照组和空白对照组。每组5只,分别皮下接种SW620细胞。造模成功后实验组、阴性对照组、空白对照组每3天分别于瘤周注射miRNA-486过表达质粒、空白载体及等量PBS,比较各组裸鼠皮下瘤体的体积,接种3周后处死裸鼠,取出皮下瘤组织,用免疫组织化学法和Western blot法分析比较neuropilin-2的表达。结果：实验组瘤体生长速度明显低于阴性对照组和空白对照组;实验组裸鼠皮下种植瘤的大小为(0.32±0.12) cm³,阴性对照组为(0.77±0.31) cm³,空白对照组为(0.82±0.18) cm³;实验组瘤体体积显著小于其他两组体积(P=0.006);实验组瘤体质量为(0.40±0.08) g,明显低于阴性对照组(0.75±0.18) g及空白对照组(0.79±0.18) g(P=0.008);实验组种植瘤中neuropilin-2的表达量较另外两组下降(P=0.000)。结论：注射miR-486过表达质粒后结直肠癌细胞SW620裸鼠皮下移植瘤的生长可受到抑制,其作用可能是通过降低neuropilin-2的表达来实现的。miR-486有望成为结直肠癌治疗新的靶点。