Effect of arsenic trioxide on the expression of VEGF of S_(180) sarcoma
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objective To explore the effect of arsenic trioxide on the expression of VEGF of S_~180 sarcoma. Methods S_~180 tumor-bearing mice were treated with different concentrations of arsenic trioxide. The contents of iNOS and NO in tumor emulsion were determined. The expression of iNOS and VEGF was measured by immunohistochemistry. Results With the concentration of arsenic trioxide increasing, the iNOS and NO contents were decreased, the expressions of iNOS and VEGF were subdued gradually, which became evident when the dose of ars enic trioxide reached 3.5 mg·kg~-1 ·d~-1 (P0.05). Conclusion It is suggested that the action of As_2O_3 may decrease the expression of of iNOS and downregulate the expression of VEGF, which in turn, may inhibit the growth of tumor vessels and the tumor growth and spread.Keywords:
Arsenic Trioxide
Trioxide
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To explore the effects of thalidomide on the expressions of vasc ular growth factors in parental and cisplatin_resistant human lung adenocarcinom a cell line A549 and A549 .Methods:RT_PCR and Immunohistochemistry were used to detect mRNA and protein expression of VEGF in A549 and A549 .Results:From t he 1st to 5 th day after treatment with physiological concentration of thalidomi de(6 mg/L),VEGF mRNA expression levels in A549 were significant higher than that before treatment.VEGF mRNA expression levels in A549 were significant lower. There were significant differences in A549 and A549 among different concentra tion of thalidomide on the 5 th day.The protein expressions were significant coi ncided with the relative VEGF mRNA expression levels in A549 and A549 .Conclus ion:Physiological concentration of thalidomide up_regulated VEGF mRNA expression significantly in A549.But large dose of thalidomide inhibits VEGF expression si gnificantly.Moreover,thalidomide down_regulated VEGF mRNA expression significant ly in A549 .It is dose_independent.The protein expression is significantly coi ncided with the relative VEGF mRNA.
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Nitric oxide (NO) has been reported to protect cells from apoptosis during chemotherapy. In this study, the protective role of inducible nitric oxide synthase (iNOS) against cisplatin (CDDP)-induced apoptosis was evaluated in a cell line and in patients with gastric cancer.MKN-45 cells were incubated with CDDP and the correlation between the occurrence of apoptotic cells (evaluated by flow cytometry) and the expression of iNOS messenger RNA (mRNA) in cells was analyzed. In 15 patients with advanced gastric cancer, CDDP-based preoperative chemotherapy was introduced. The expression levels of iNOS mRNA were compared between tumor samples before and after treatment with CDDP. Moreover, the iNOS protein expression and the percentage of apoptotic cancer cells (apoptotic index: AI) were analyzed immunohistochemically in 15 CDDP-treated tumors and in 50 untreated advanced gastric cancers.High AI was detected after 24 hours of treatment with high-dose CDDP in MKN-45, while the iNOS mRNA expression levels did not change before and after treatment. In 15 patients treated with CDDP, the percentage of iNOS mRNA-positive cases increased from 20% (pretreatment tumors) to 40% (resected tumors). However, the mean AI of iNOS-positive tumors was not different from that of iNOS-negative tumors. Also, in 50 untreated patients, iNOS protein expression did not correlate with the AIs of the tumors.Our results demonstrate that iNOS expression may not correlate with the occurrence of apoptosis during CDDP treatment in gastric cancer.
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Aim To observe the regulatory effect of LZBZY on the growth of H22 tumor and the expression of vascular endothelial growth factor(VEGF) in transplanted H22 tumor of mice,and explore whether the inhibition of tumor is related to the inhibition of vascular growth.Methods The mice were vaccinated with H22 cells suspension(1×107/ml) 0.2 ml each one.The observation was made on the weight of the transplanted tumor of the mice,then the inhibitory rate was calculated.The expression of VEGF was determined by the immunohistochemical method.Results The LZBZY group had significant effect on inhibiting the tumor growth(P0.05,P0.01),when compared with the model group,the pathological detective results showed that the positive rate of expression of VEGF was 100% in each group with the degree difference.Moreover,the expression of VEGF was decreased obviously in LZBZY group(P0.05,P0.01).Conclusion The LZBZY can inhibit the growth of the transplanted H22 tumor of mice and decrease the expression of the VEGF.
Normal group
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Objective To study the inhibitory effects of Protopanaxidiol(Ppd) on vascular endothelial growth factor(VEGF) and its mRNA expression of liver cancer.Methods Liver cancer model animals were divided into control group,positive drug group,cyclophosphamide group,low,medium and high dosage of Ppd group(25,50,100 mg/kg),10 ones in each group.After two weeks,the animals were killed to make histological section for immunohistochemical and hybridization in situ stain.Results Control group had increased tumor interstitial vessel density,the enhanced VEGF and mRNA expression positively relating to vessel density,while Ppd treatment group had decreased above indexes(P0.01);and medium and high dosage of Ppd had stronger inhibitory effect than cyclophosphamide(P0.01).Conclusions Ppd inhibits VEGF and its mRNA expression in tumor tissue and tumor angiogenesis,thus inhibits tumor growth.
Liver Cancer
Stain
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This study was aimed to investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 in gastric cancer in order to clarify the role of As2O3 in lymphangiogenesis and metastasis of tumor. The gastric cancer model was established in nude mice by using gastric cancer cell line SGC-7901. As2O3 was injected to the two treatment groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected to the control group. Expression of VEGF-C and VEGFR-3 were detected by immunohistochemistry and were analyzed with QWin550cW image Acquiring & Analysis System. The results showed that the expression of VEGF-C and VEGFR-3 in cancer cells significantly reduced in the arsenic -treated groups. The expression of VEGF-C and VEGFR-3 in 5 mg/kg group was significantly less than that in 2.5 mg/kg group. The gray ratio analysis confirmed that there were significant difference between control group and two treated group, as well as between 2.5 mg/kg-treated group and 5 mg/kg-treated group. It is concluded that As2O3 can inhibit expression of VEGF-C and VEGFR-3 of human gastric cancer xenografts in nude mice, which suggests that As2O3 may inhibit the lymphangiogenesis by suppressing the expression of VEGF-C and VEGFR-3.
Arsenic Trioxide
Lymphangiogenesis
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Objective To investigate the effect of Vitamin C on the anti-cancer roles of arsenic trioxide(AS2O3) and the possible mechanism.Methods A549 cells cultured in vitro were divided into 6 groups randomly.The control gruop was given no especial treatment,and AS2O3 1-3 group were treated with AS2O3 at the concentration of 0.4,4.0,40 μg/ml,the Vitamin C gruop was treated with Vitamin C of 400 μg/ml,the combined group was treated with Vitamin C of 400 μg/ml+0.40 μg/ml AS2O3.The cell proliferation(A value)was measured by CCK-8 assay and clonogentic assay,the cell cycle and apoptosis were detected by flow cytometry,the expressions of Caspase-3 mRNA,MRP1 mRNA,MDR1 mRNA were measured by RT-PCR assay(Vitamin C group).Results The absorbance of the combined group and AS2O3 2-3 groups were significantly lower than that of the AS2O3 1 group and Vitamin C group,which decreased gradually with the time extension(P0.05).The cell colony of the combined group was significantly fewer than that of the other groups,while the percentage of G0/G1 and apoptosis were significantly higher(P0.05).The expression of Caspase-3 mRNA and MDR1 mRNA of the Vitamin C group increased(P0.05),the expression of MRP1 mRNA showed no significant changes(P0.05).Conclusion Vitamin C has synergistic action on the anti-lung adenocarcinoma roles of AS2O3,possible mechanism is related to the up-ragulation of the expression of Caspase-3 mRNA.Application of Vitamin C and AS2O3 might be a chemotherapy combination with low toxicity and efficient.
Arsenic Trioxide
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Objective To study the effect of arsenic trioxide(As\-2O\-3) combind with interferon(IFNα\|2b) on multidrug\|resistance of K562 and K562/ADM cell lines. Methods Immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling(TUNEL) were used to detect the expression of P\|gp, GST\|π and Bcl\|2, and the induction of apoptosis by As\-2O\-3 at different doses and time or combined with IFNα\|2b. Results The expression of P\|gp did not change; the expression of GST\|π was decreased(P0 05 vs contrast) following treatment 72 h with arsenic trioxide(5, 10, 20 μmol/mL); the expression of Bcl\|2 was decreased and the number of apoptotic cells increased, which enhanced with the increment of arsenic trioxide dosage and time, the effect was more prominent in IFN combined with As\-2O\-3 for K562 cell. Conclusion Arsenic trioxide may suppress the expression of GST\|π, Bcl\|2 and induce apoptosis of K562, K562/ADM cell lines, and did not affect expression of P\|gp. IFN might enhance the effect of As\-2O\-3 on K562 cells.
Arsenic Trioxide
K562 cells
Terminal deoxynucleotidyl transferase
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Objective To study the effect and mechanism of arsenic trioxide(AS2O3) combined with Vitamin C on the subcutaneously transplanted tumor of drug resistant human lung carcinoma in nude mice.Methods The subcutaneously transplanted tumor models of drug resistant human lung carcinoma in nude mice were established and then were divided into NS,Vit C(250 mg/kg),1.5,3 mg/kg AS2O3,and combining AS2O3 with Vit C groups.They were injected intraperitoneally two weeks.The weight of mice and volume of tumor pre-and post-administration were measured.All mice were killed after administration and the mass of tumor was measured and tumor inhibition was calculated.Immunohistochemical staining was used to observe the expressions of Caspase-3 and Survivin protein.RT-PCR and Western blot were used to detect the expressions of Caspase-3 and Survivin.Results The tumor inhibitory rate of Vit C,1.5,3 mg/kg AS2O3,and combining AS2O3 with Vit C were 3.47%,42.3%,66.25%,79.93%.The volume,mass of tumor were decreased after treatment.Compared with NS group,the differences were significant(P0.01).The tumor mass and volume were decreased in the test groups,and effects of the combined drug group was better than that of single-drug groups.Moderate necrosis was found in tumor tissues,and Caspase-3 protein positive rate was increased,Survivin protein positive rate reduced.The expressions of Survivin mRNA and protein in the combination group were markedly lower than those of the other groups and the expression of Caspase-3 mRNA was higher.Conclusions AS2O3 combined with Vit C has stronger inhibition effect on tumor growth than single use of one drug.AS2O3 and Vit C have a synergic anticancer effect on transplanted lung cancer in nude mice,which possible mechanism is related to down-regulation of the expression of Survivin and up-regulation of the expression of Caspase-3.Application of Vit C and AS2O3 might be a chemotherapy combination with low toxicity and efficient.
Arsenic Trioxide
Survivin
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Objective
To investigate the inhibitory effect and mechanism of arsenic trioxide on hepatocellular carcinoma (HCC) cells migration induced by low dose of sorafenib.
Methods
Human HCC cells MHCC97H in logarithmic phase were treated with 2 μmol/L arsenic trioxide (arsenic trioxide group), 3 μmol/L sorafenib (sorafenib group), 2 μmol/L arsenic trioxide + 3 μmol/L sorafenib (combination group), 50 μmol/L LY294002(LY group) and 3 μmol/L sorafenib + 50 μmol/L LY294002 (LY+ sorafenib group) respectively. Dimethyl sulfoxide (DMSO) was used in the control group. Wound healing assay and Transwell migration assay were used to detect the ability of horizontal and vertical cell migration. The expression of p-Akt, E-cadherin, Vimentin and Snail proteins was measured by Western blot. The experiment data were compared using one-way ANOVA and Bonferroni test.
Results
Wound healing assay revealed that the horizontal migration speed in the sorafenib, arsenic trioxide and combination groups was (1.59±0.14), (0.39±0.08) and (0.58±0.12) times of that in the control group (t=7.20, -12.58, -6.62; P<0.05). Transwell migration assay revealed that the number of cells in the sorafenib, arsenic trioxide, combination and control groups was 285±26, 169±18, 194±19 and 228±9 respectively. Compared with the control group, the number of cells was significantly increased in the sorafenib group (t=3.48, P<0.05), whereas significantly decreased in the arsenic trioxide group (t=-3.80, P<0.05). The number of cells in the combination group was significantly decreased than that in the sorafenib group (t=-5.67, P<0.05). Western blot revealed that the expression of p-Akt, Snail and Vimentin proteins was up-regulated, whereas the expression of E-cadherin protein was down-regulated in the sorafenib group compared with those in the control group. Compared with the control group, the expression of p-Akt, Snail and Vimentin proteins was down-regulated whereas the expression of E-cadherin protein was up-regulated in the arsenic trioxide, combination, LY and LY + sorafenib groups.
Conclusion
Arsenic trioxide can inhibit the epithelial-mesenchymal transition and reverse the promoting effect of low-dose sorafenib upon MHCC97H cell migration through suppressing the activation of PI3K/Akt/Snail signaling pathway.
Key words:
Carcinoma, hepatocellular; Sorafenib; Arsenic trioxide; Epithelial mesenchymal transition
Arsenic Trioxide
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