Advances in zebrafish models of tumor / 中国药理学通报

Zebrafish, with unique characteristics, has been widely involved in the study of the occurrence and development of tumors, the development and screening of anti-tumor drugs, and the determination of the best treatment regimen.In this review, we highlight and raise awareness regarding the classification, characteristics and advantages of zebrafish tumor models, helping to understand and apply zebrafish tumor models reasonably.

Lentivirus mediated RNAi silence esophageal MDC1 Eca109 cell gene expression of the influence of nude mouse transplantation tumor radiosensitivity / 中华放射肿瘤学杂志

Objective To investigate the effects of inhibition of MDC1 protein expression on xenografted tumors in nude mice,and to observe the histopathological and cellular changes in nude mice.Methods Three pairs of effective and control short hairpin RNA targeting MDC1 mRNA were designed and cloned into the pSIH1-H1-copGFP vector.Real-time PCR and Western blot were used to determine the mRNA and protein expression of MDC1.After selection by copGFP reporter gene,cells were divided into negative transfection group (ECA109-N) and MDC1 transfection group (ECA109-M).The transfected cells were injected into nude mice.The mice were divided into ECA109 group,ECA109-N group,and ECA109-M group.Each group was divided into irradiation subgroup and non-irradiation subgroup.The changes in tumor size after irradiation were evaluated in each group.Western blot was used to measure the expression of CHK1,CHK2,and CHK2T68 in xenografted tumors.Flow cytometry was used to analyze the cell cycle distribution and apoptosis of tumor cells in nude mice.The variance analysis was used to compare the mean of multiple groups,and the SNK-q test was used in the two two groups.Results The pMDC1-shRNA plasmid was successfully constructed and used to transfect ECA109 cells.ECA109-M cells were obtained by stable transfection with the recombinant plasmid.All inoculated nude mice survived with visible xenografted tumors at the underside of the paw in about one week.There was no swelling and wound in inoculation sites.There was no significant difference in tumor size between different groups (P＞0.05).The tumor growth in the ECA109 group and the ECA109-N group significantly slowed down after irradiation with a dose of 15 Gy (P＜0.05).Compared with the other two groups,the ECA109-M group had a significant smaller tumor size,significantly slower relative tumor growth,and significantly higher growth inhibition (all P＜0.05).The q value of the ECA109-M group was 1.36.In the ECA109-M group,there were no significant changes in the protein expression of CHK1 and CHK2 after irradiation (P＞ 0.05);however,the phosphorylation of CHK2T68 protein was significantly reduced after irradiation (P＜0.05).There were no significant differences in cell cycle distribution or the proportion of apoptotic cells in tumor tissue between the three groups (P＞0.05).Conclusions Inhibition of MDC1 protein expression by RNA interference can effectively inhibit the growth of xenografted tumors after irradiation in the nude mice by increasing their radiosensitivity.

Study on Anti-lung Cancer Efficiency of Centipede Extracts in Vitro and Vivo Experiments / 中国中医药信息杂志

Objective To investigate efficiency of centipede extracts on apoptosis induction, proliferation inhibition to Human A549 cell line and growth suppression of subcutaneous transplanted sarcoma in nude mice. Methods Centipede extracts prepared by enzymolysis and acetone precipitation methods were used to treat human lung cancer A549 cell line. Proliferation inhibition was evaluated by MTT assay and half inhibit concentration (IC50) was calculated. Cell morphological change and apoptosis were detected by flow cytometry and Hoechst stain. The subcutaneous transplanted sarcoma models were prepared with nude mice and randomly divided into model group, control group and centipede extracts group, with 10 mice in each group. Changes of tumor volume, quality and anti-tumor rate were observed.Results In vitro experiment, proliferation of A549 cells was inhibited with dose-dependency and IC50 value was 0.603 mg/mL. The G0/G1 phase of cells was down regulated and G2/M and S phase cells were up-regulated. The apoptotic character cells were been found by Hoechst stain. In vivo experiment, the tumor weight and volume decreased significantly compared with model control group, with statistical significance (P<0.01).Conclusion The centipede extracts shows dose-dependent anti-proliferative effect on A549 cells, which can induce apoptosis by arresting A549 cells at G2/M phase and suppressing growth of subcutaneous transplanted sarcoma of lung cancer in nude mice.

Study on anti-tumor activities of ginsenoside structure modification HRG in vivo / 中国药学杂志

OBJECTIVE: To explore the anti-tumor activities of a new compound 3β,12β,20(S)-trihydroxy dammarane-3-O-β-D-glucopyranosyl (1-2)-β-D-glucopyranoside (HRG), which is a substance of ginsenoside structure modification, in vivo. METHODS: Liver cancer H22 tumor model on the chick chorioallantoic membrane (CAM) was established to observe the effects of HRG on tumor growth, the number of induced vessels and the growth inhibition rate. The implanted tumors were dyed by hematoxylin-eosin (HE), and the morphological properties were studied with light microscope. Immunohistochemistry (SP method) was used to detect the expressions of the implanted tumor's MVD and VEGF. RESULTS: HRG inhibited the tumor growth at 25, 50 and 100 μg · mL-1. Compared with the model control group, the inhibitory rates of the tumor growth were 27.73%, 50.02%, and 64.21%, respectively. HRG significantly reduced the number of tumor-induced vessels. At the same time, there existed different degree necrosis among the treatment groups, and the degree of necrosis had an inverse relationship with the number of tumor-induced vessels. In addition, HRG reduced the MVD of the implanted tumors, and decreased the expression of VEGF. CONCLUSION: HRG has good anti-tumor activities in vivo, and can significantly inhibit the growth of liver cancer H22-CAM tumor and the induction of angiogenesis. The mechanisms may be associated with lower tumor MVD and VEGF expression.

Experimental Study of Multiple-Mouse MRI in Evaluating the Therapeutic Effect of Endostatin for Colorectal Carcinoma in Mice / 实用放射学杂志

Objective To explore the value of multiple-mouse MRI in evaluating the therapeutic effect of endostatin for transplantation tumor models of colorectal carcinoma in mice.Methods 24 subcutaneously transplantation tumor’s models of colorectal carcinoma (CT-26) in mice were established, 1 week later, 16 tumor-bearing mice were sieved out and divided randomly into two groups: endostatin (ES) group and normal saline (NS) group, treated with intraperitoneal injection of endostatin 6 mg/kg?d 0.2 ml and equal volume of saline respectively for 14 days. Subsequently, MMMRI was performed, and then the mice were killed immediately and the tumors were cut into sections which were stained with hematoxylin and eosin (H&E). Results Subcutaneous fat layer in NS group presented thinner or disappeared on T1WI,while subcutaneous fat layer in ES group presented thicker. The tumors presented inhomogeneous high signal and intratumoral stippled necrosis on T2WI. The tumor’s volumes measured by MRI and pathology were(2723.26?1136.91) mm3 and (3505.76?1350.12) mm3 respectively,there was no difference between these two measures. And there was correlation between MRI results and pathological results. There was no difference of absolute signal intensity between ES group and NS group on T1WI and T2WI. The signal intensity ratio of ES group (3.19?0.28) was higher than which of NS group (2.60?0.47) on T2WI, and there was no difference on T1WI. Conclusion The therapeutic effect for endostatin on transplantation tumor models of colorectal carcinoma in mice can be displayed distinctly in MMMR image, and the inhibition rate of results can be displayed exactly and noninvasively.

Cytokine-induced killer cells specifically inhibits implanted gastric cancer cells / 中国肿瘤生物治疗杂志

Objective:To investigate the inhibitory effect of cytokine-induced killer cells (CIK) against implanted gastric cancer cells. Methods:Gastric cancer SGC-7901 cells were subcutaneously injected into the inguina of nude mice to establish gastric cancer model. The tumor bearing mice were randomly divided into CIK group and fibroblasts group,in which mice were subcutaneously injected with fluorescence dye SP-DiI labeled CIK and fibroblasts HFL-I cells,respectively. Distribution of CIK and HFL-I cells in different tissues of gastric cancer bearing mice were observed. Meanwhile,tumor volume was measured after different treatments and tumor inhibitory rate was calculated. Tumor necrosis areas in different groups were observed. Results:SP-DiI labeled CIK was mainly located in the gastric cancer tissues 10 d after injection,and was hardly detected at the injection sites,liver,spleen and lung tissues (P