Font Size: a A A

Study Of Antineoplastic Activity Of PPAR-γ Ligand RGZ On QBC 939 Cell Line Of Human Cholangiocarcinoma In Nude Mice In Vitro And In Vivo

Posted on:2008-02-01Degree:MasterType:Thesis
Country:ChinaCandidate:L H WuFull Text:PDF
GTID:2144360218460098Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: To investigate the effect that PPAR-γ(peroxisome proliferactor-activated receptor gamma, PPAR-γ) ligand Rosiglitazone (Rosiglitazone, RGZ) inhibits the cell proliferation of cholangiocarcinoma.Method: Interfered the cell line QBC939 of cholangiocarcinoma with different concentrations of RGZ, then calculated the QBC939 cell inhibit-tion ratio in different groups and drawed the proliferation inhibition curve; detected the changes of cell cycle and the ratio of apoptosis in each concen-tration by FCM (flow cytometry, FCM); finaly, statisticed the results.Result: RGZ has the significant effect in inhibiting the cell proliferation of cholangiocarcinoma, especially in the concentration of 1.2mg/ml group, the highest proliferation inhibition ratio could be up to 83.66%; meanwhile, the cell cycles are controlled significantly as well, 62.77% of the total cells were detained in stage G0/G1. 1.2mg/ml and 0.6mg/ml groups show a significantely higher inhibition ratio than low dose group and control group, P<0.001.Conclusion: PPAR-γligands Rosiglitazone have the significant proliferation inhibition effect to cell lines QBC939 of cholangiocarcinoma in vitro experiment. Objective: To detect the effective ways of that PPAR-γligand RGZ inhibit the proliferation on cholangiocarcinoma in vivo.Method: Gave the RGZ to the nude mice bearing cancer of cholangiocarcinoma (QBC939) by four ways for one week, then measured of the the volumes and weights of the tumors and evaluated the inhibition ratio of the tumor growing.Result: RGZ could only show the best inhibition of tumor growing in nude mice experimented group 5, while the other RGZ experimented groups and control group had no effect to the transplantation tumor of cholangiocarcinoma in nude mice. Statistic data showed there was an obviously role of decreasing the volume and the weight of the transplantation tumor in group 5 compared with the control group, P<0.05; but the other groups did not show any significances compared with control group, P>0.05.Conclusion: RGZ can effectively decrease the volume and the weight of QBC939 transplantation tumor in nude mice. But the ways of drug giving have the different results. Only continuing multi-intragatric administration method could significantly decrease the volume and the weight of transplantation tumumor. Objective: To study the effect of PPAR-γligand RGZ on expression in QBC939 transplantation tumor in vivo.Method: Interfered the nude mice bearing cancer of Cholangiocarcinoma with RGZ in different concentration and dosages, then fed RGZ trough the way of multi-intragastric administration for 3 weeks. Measured the tumor volumes and weights, evaluated the relative tumor volume, relative tumor increasing ratio T/C%; detected the expression of PPAR-y by RT-PCR by Real Time Fluorescent Quantitation and statistic analysis as well.Result: There was a PPAR-γ-mRNA expression in all transplantation tumor of nude mice. But its expression levels increased along with the increasing dosage of RGZ. Meanwhile, the volumes, weights, the relative tumor increment ratio T/C% of the transplantation tumor decreased. Statistic treatments showed there was no significance between control and low RGZ dose groups, P>0.05; but there was an obviously difference between the high RGZ dose groupand control/lower RGZ dose group, P<0.001.Conclusion: In vivo experiment, the RGZ can show an obvious effect of up-regulation of PPAR-γexpression in transplantation tumor of nude mice. Objective: To study the Antineoplastic activity of PPAR-γligand rosiglitazone (RGZ) on nude mice transplantation tumor of Cholangiocarcinoma QBC939.Method: Estabolished the nude mice transplantation models of QBC939. 7 days later, the mice were given RGZ in different concentration and dosage, through the ways of intragastric administration (once a day for three weeks). Evaluated the volumes and weights of the tumor, the relative tumor volume (RTV), the relative tumor increasing ratio T/C% of transplantation tumor; Detected the expression level of PPAR-γby RT-PCR, and apoptosis by TUNEL. Detected the expression level of CD34 by SP-immunohistochemistry and evaluated the MVD, statistic analysised as well.Result: Following the raising of the dose of RGZ, the expression level of PPAR-γ-mRNA and the apoptosis ratio of the tumor cells increased, while the volumes and the weights of the tumor, the relative tumor increasing ratio T/C%, the expression level of CD34, the MVD decreased in the transplantation tumor. Statistic treatments showed there was no significance between control and low dose groups, P>0.05; but comparing with the lower dose groups and control group, the high group showed an obviously significance, P<0.001.Conclusion: In vivo, applying 10 times or more dosage than human, RGZ can show an obvious tumor inhibition and good antineoplasmic activities on transplantation tumor in mice model.
Keywords/Search Tags:PPAR-γ, RGZ, cell proliferation inhibition, apoptosis, the ways of dosage, cholangiocarcinoma, RGZ, Cholangiocarcinoma gene expression, RGZ, Cholangiocarcinoma, Antineoplastic activity
PDF Full Text Request
Related items