ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of sorafenib and liposome doxorubicin on poorly differentiated thyroid carcinoma (PDTC) xenografts in nude mice.</p><p><b>METHODS</b>Sorafenib and liposome doxorubicin were applied to PDTC xenografts in nude mice. The mice were randomized into seven groups: blank control (A), vehicle control (B), single liposome doxorubicin (C), single sorafenib group (D), liposome doxorubicin combined with low dose sorafenib group (E), combined group with medium dosage of sorafenib (F), combined group with high-dose of sorafenib(G). The volume, weight and growth inhibition rate of tumours were measured to evaluate the therapeutic effects of drugs.</p><p><b>RESULTS</b>Sorafenib and liposome doxorubicin showed significant antitumor activity in the PDTC xenografts. The mean tumor volumes of seven groups were (1274.13 ± 393.76) mm(3), (1060.00 ± 469.05) mm(3), (726.76 ± 488.22) mm(3), (451.54 ± 97.75) mm(3), (518.37 ± 164.44) mm(3), (310.51 ± 210.53) mm(3), and (228.44 ± 129.21) mm(3), respectively. The mean tumor weights of the seven groups were (1.13 ± 0.42)g, (0.91 ± 0.39)g, (0.78 ± 0.45)g, (0.55 ± 0.17) g, (0.52 ± 0.19) g, (0.34 ± 0.21) g, and (0.19 ± 0.09) g separately. The tumor inhibition rates of group C to G were 30.8%, 40.8%, 42.3%, 62.9%, 72.6% separately.</p><p><b>CONCLUSIONS</b>Sorafenib and liposome doxorubicin, no matter for single agent or in combination, showed significant antitumor activity in the PDTC PDTC xenografts in vivo. The tumour-inhibited effect of single sorafenib is better than that of single liposome doxorubicin. Liposome doxorubicin combined with medium dosage of sorafenib had a better therapeutic effect and less side effects.</p>
Subject(s)
Animals , Humans , Mice , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Doxorubicin , Liposomes , Mice, Nude , Niacinamide , Phenylurea Compounds , Thyroid Neoplasms , Drug Therapy , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of pcDNA3.1-Egr.1p-p16 plasmid on apoptosis and cell cycle of pancreatic carcinoma JF305 cell line.</p><p><b>METHODS</b>JF305 cells were cultured and transfected with pcDNA3.1-Egr.1p-p16 plasmid via Lipofectamine(TM) 2000, followed by irradiation by 6MV-X at 4 Gy (dose rate 2.50 Gy/min). The cell cycle and cell apoptosis changes were analyzed by flow cytometry.</p><p><b>RESULTS</b>In cells infected with pcDNA3.1-Egr.1p-p16 plasmid and those with pcDNA3.1-Egr.1p-p16 plasmid infection before 4 Gy irradiation, the percentages of viable apoptotic cells were 6.4% and 10.4%, and those of advanced stage apoptotic or dead cells were 16.8% and 33.8%, significantly higher than those in the control group (P<0.05). JF305 cell apoptosis in 4 Gy irradiation group was obviously increased in comparison with non-irradiated plasmid-infected cells (P<0.05). Irradiation resulted in a predominant G(2) arrest of the plasmid-infected JF305 cells. Both pcDNA3.1-p16 plasmid and pcDNA3.1-Egr.1p-p16 plasmid infections could induce G1 arrest of JF-305 cells, and irradiation did not produce significant changes in G(1)-arrested cells in the two plasmid infection groups, but cells arresting at G(2) phase increased.</p><p><b>CONCLUSION</b>pcDNA3.1-Egr.1p-p16 can induce JF-305 cells apoptosis, which is enhanced by irradiation. pcDNA3.1-Egr.1p-p16 tranfection may result in G(1) arrest of the cells, and when combined with irradiation, the cells arrested at G(2) phase can increase.</p>
Subject(s)
Animals , Humans , Apoptosis , Genetics , Radiation Effects , Cell Cycle , Genetics , Radiation Effects , Cell Line, Tumor , Genes, p16 , Genetic Therapy , Plasmids , Genetics , Radiation Dosage , Radiotherapy , Time Factors , TransfectionABSTRACT
OBJECTIVE@#To investigate the optimal doses of X-ray irradiation and plasmid injection in the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in vivo.@*METHODS@#We observed the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy with different doses of X-ray irradiation (2, 10, 20 Gy) and plasmid injection (10, 20, 30 microg) in nude mice with JF-305 pancreatic carcinoma, and detected the expression of p16 in tumor by RT-PCR.@*RESULTS@#The tumor growth rate of the nude mice irradiated locally with 20 Gy X-rays after the plasmid injection was significantly lower (P < 0.05 ) than that of the nude mice irradiated locally with 2 Gy or 10 Gy X-ray 3 days after the irradiation. The tumor growth rate of the nude mice injected locally with 20 microg or 30 microg plasmid was significantly lower (P <0.05 ) than that of the nude mice injected locally with 10 microg plasmid. Both pcDNA3. 1-Egr. 1p-p16 group and pcDNA3. 1-Egr. 1p-p16 +20 Gy group had p16 mRNA expression, but the mRNA level of pcDNA3. 1-Egr. 1p-p16 +20 Gy group was higher than that of pcD- NA3. 1-Egr. 1p-p16 group.@*CONCLUSION@#In the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in vivo the optimal dose of X-ray irradiation was 20 Gy and the optimal dose of plasmid injection was 20 microg. The anti-tumor effect of pcDNA3. 1-Egr. 1p-p16 combined with radiotherapy is better than that of radiotherapy or gene therapy alone, which may be related with the enhanced p16 expression in tumor after the irradiation.
