[Inhibitory Effect of Ginsenoside Rg3 Combined With 5-Fluorouracil on Tumor Angiogenesis and Tumor Growth of Colon Cancer in Mice: An Experimental Study]. / 人参皂苷Rg3与5-æ°Ÿå°¿å˜§å•¶è”ç”¨å¯¹ç»“è‚ ç™Œå°é¼ è‚¿ç˜¤çš„è¡€ç®¡ç”Ÿæˆä¸Žè‚¿ç˜¤ç”Ÿé•¿æŠ‘åˆ¶æ•ˆæžœçš„å®žéªŒç ”ç©¶.

Objective: To evaluate the inhibitory effect of ginsenoside Rg3 combined with 5-fluorouracil (5-FU) on tumor angiogenesis and tumor growth in colon cancer in mice. Methods: CT26 mouse model of colon cancer was established and the mice were randomly assigned to the control group, the ginsenoside Rg3 group, the 5-FU group, and the Rg3 combined with 5-FU group. The 5-FU group was injected intraperitoneally at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 10 days. Treatment for the Rg3 group was given at the dose of 20 mg/kg, 0.2 mL/animal, and once a day for 21 days via gastric gavage. The dose and the mode of treatment for the Rg3+5-FU combination group were the same as those for the 5-FU and the Rg3 group. The control group was intraperitoneally injected with 0.2 mL/d of normal saline for 10 days. The expression of vascular endothelial growth factor (VEGF) and CD31 and the microvascular density (MVD) of the tumor tissues were examined by immunohistochemistry. The blood flow signals and tumor necrosis were examined by color Doppler flow imaging (CDFI). The quality of life, survival rate, tumor volume, tumor mass, and tumor inhibition rate of the mice were monitored. Results: After 21 days of treatment, the tumor volume and the tumor mass of all treatment groups were significantly decreased compared with those the control group, with the combination treatment group exhibiting the most significant decrease. The tumor inhibition rates of the Rg3 group, the 5-FU group, and the combination group were 29.96%, 68.78%, and 73.42%, respectively. Rg3 treatment alone had inhibitory effect on tumor growth to a certain degree, while 5-FU treatment alone or 5-FU combined with Rg3 had a stronger inhibitory effect on tumor growth. The tumor inhibition rate of the combination group was higher than that of the 5-FU group, but the difference was not statistically significant (P>0.05). Color Doppler ultrasound showed that there were multiple localized and large tumor necrotic areas that were obvious and observable in the Rg3 group and the combination group, and that there were only small tumor necrotic areas in the 5-FU group and the control group. The tumor necrosis rate of the combination group was (55.63±3.12)%, which was significantly higher than those of the other groups (P<0.05). CDFI examination of the blood flow inside of the tumor of the mice showed that the blood flow signals in the combination group were mostly grade 0-Ⅰ, and that the blood flow signals in the control group were the most abundant, being mostly grade Ⅱ-Ⅲ. The abundance of the blood flow signals in the Rg3 and 5-FU groups were between those of the control group and the combination group. Compared with those of the control group, the expression levels of MVD and VEGF in the tumor tissues of the Rg3 group, the 5-FU group, and the combination group were significantly decreased, with the combination group showing the most significant decrease (P<0.05). HE staining results indicated that there was significant tumor necrosis in mice in the control group and that there were more blood vessels. In contrast, in the tumor of the Rg3 group and the 5-FU group, there were fewer blood vessels and necrotic gaps appeared within the tumors. In the combination group, the tumor tissues had the fewest blood vessels and rope-like necrosis was observed. The mice started dying on the 18th day after treatment started, and all the mice in the control group died on the 42nd day. By this time, there were 3, 5, and 7 mice still alive in the Rg3 group, the 5-FU group, and the combination group, respectively, presenting a survival rate of 30%, 50%, and 70%, respectively. All mice in all the groups died on day 60 after treatment started. Conclusion: Ginsenoside Rg3 combined with 5-FU can significantly inhibit tumor angiogenesis and tumor growth of colon cancer in mice and improve the survival and quality of life of tumor-bearing mice.

Inhibitory effect of Bifidobacterium infantis-mediated sKDR prokaryotic expression system on angiogenesis and growth of Lewis lung cancer in mice.

BACKGROUND: To construct the Bifidobacterium infantis-mediated soluble kinase insert domain receptor (sKDR) prokaryotic expression system and to observe its inhibitory effect on growth of human umbilicus vessel endothelial cells (HUVECs) in vitro and Lewis lung cancer (LLC) on mice in vivo. METHODS: The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed through electroporation and subsequently identified through PCR and Western blot analysis. HUVECs were added to the products of this system to evaluate the anti-angiogenesis effect through MTT assay in vitro. The LLC mice models were divided into three groups: one group treated with saline (group a); one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT plasmid group (group b); and one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid group (group c). The quality of life and survival of mice were recorded. Tumor volume, tumor weight, inhibitive rate, and necrosis rate of tumor were also evaluated. Necrosis of tumor and signals of blood flow in tumors were detected through color Doppler ultrasound. In addition, microvessel density (MVD) of the tumor tissues was assessed through CD31 immunohistochemical analysis. RESULTS: The positively transformed Bifidobacterium infantis with recombinant pTRKH2-PsT/sKDR plasmid was established, and was able to express sKDR at gene and protein levels. The proliferation of HUVECs cultivated with the extract of positively transformed bacteria was inhibited significantly compared with other groups (P < 0. 05). The quality of life of mice in group c was better than in group a and b. The recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid enhanced the efficacy of tumor growth suppression and prolongation of survival, increased the necrosis rate of tumor significantly, and could obviously decrease MVD and the signals of blood flow in tumors. CONCLUSION: The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed successfully. This system could express sKDR at gene and protein levels and significantly inhibit the growth of HUVECs induced by VEGF in vitro. Moreover, it could inhibit tumor growth and safely prolong the survival time of LLC C57BL/6 mice.

Association of the Glutathione S-transferase T1 Null Genotype with Risk of Gastric Cancer: a Meta-analysis in Asian Populations.

BACKGROUND: A large number of studies have been published to investigate the association between the null genotype of glutathione S-transferase T1 (GSTT1) with gastric cancer. However, the results were inconsistent and conflicting. The aim of this study was to estimate the relationship between this polymorphism in the GSTT1 gene and gastric cancer risk in Asian populations by meta-analysis. MATERIALS AND METHODS: A literature search was performed in PubMed, Embase, Chinese Biomedical database (CBM), Weipu database, Wanfang database, and China National Knowledge Infrastructure database (CNKI). Statistical analysis was conducted by using Review Manager 5.3. RESULTS: Thirty-nine studies with a total of 7,737 gastric cancer cases and 10,823 controls were included in this meta-analysis. The meta-analysis of total studies showed that the null genotype in GSTT1 was associated with increased risk of gastric cancer in Asians (OR=1.19, 95% CI=1.08-1.31, p=0.0002). Subgroup analysis showed a significant relationship between GSTT1 null genotype and gastric cancer in East-Asians, as well as in subgroup analysis of hospital-based design. On subgroup analysis by smoking status, alcohol status, Helicobacter pylori infection status, and histology type, no significant association of this polymorphism with susceptibility to gastric cancer was found. CONCLUSIONS: In conclusion, the results showed that the null genotype of GSTT1 is significantly associated with an increased risk in gastric cancer in Asian populations.

The synergistic effects of low-dose irinotecan and TRAIL on TRAIL-resistant HT-29 colon carcinoma in vitro and in vivo.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily that induces apoptosis in a broad range of human cancer cell lines while sparing most normal cell types. However, many tumors remain resistant to treatment with TRAIL. In this study, we investigated the synergistic effects of low-dose irinotecan (CPT-11) and TRAIL on TRAIL­resistant HT-29 colon carcinoma cells and explored potential mechanisms of apoptosis. Cell viability was analyzed by sulforhodamine B (SRB) assay and apoptosis was evaluated by flow cytometry and DNA ladder assay. The mRNA expression of TRAIL receptors death receptor 4 (DR4) and DR5 were determined by reverse transcription polymerase chain reaction (RT-PCR). The changes of Bax and caspase-9 in protein levels were also detected by western blotting. Tumor growth curves were depicted and tumor inhibitive rates were calculated. Our results showed that the antitumor effect of TRAIL could be enhanced significantly by low-dose CPT-11 on TRAIL-resistant HT-29 cells both in vitro and in vivo. The synergistic apoptotic effect of CPT-11 and TRAIL was proposed to be mediated by upregulating DR5 mRNA expression and increasing expression of Bax and caspase-9 proteins. The data suggest that the combination of TRAIL with low-dose CPT-11 could be an effective therapeutic approach for HT-29 colon carcinoma.