Objective: To evaluate transduction efficiency with recombinant adenovirus-mediated p53 (rAd/p53) therapy in a human colon cancer mouse model by intra-tumoral injection and intra-arterial delivery. Methods: The tumor ...Objective: To evaluate transduction efficiency with recombinant adenovirus-mediated p53 (rAd/p53) therapy in a human colon cancer mouse model by intra-tumoral injection and intra-arterial delivery. Methods: The tumor pieces of human colon cancer SW480 were implanted in the livers of 45 nude mice. These mice were administrated with rAd/p53 by intratumoral injection and intra-arterial delivery. After 24 h, 48 h and 72 h rAd/p53 administration, 5 mice each group were killed with over anesthesia and their livers were removed. P53 expression and apoptosis of tumor and liver were assessed. Results: P53 expression and apoptosis of intratumoral administration group was higher than tail vein group and control group. Apoptosis and p53 expression of livers in three groups had no significant difference. Conclusion: p53 gene transduction efficiency and anticancer effect of rAd/p53 is much better by intra-tumoral injection than intra-arterial delivery.展开更多
AIM:To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy.METHODS:Three gastric cancer cell lines with distinct levels of differentiati...AIM:To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy.METHODS:Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone,oxaliplatin(OXA) alone,or a combination of both.Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay and the expression levels of p53,Bax and Bcl-2 were determined by immunohistochemistry.The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry.RESULTS:Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time-and dosedependent manner;moreover,significant synergistic effects were observed when these treatments were combined.Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone,OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells.Furthermore,flow cytometry showed that rAd-p53 alone,OXA alone or combination treatment induced apoptosis of gastric cancer cells,which was accompanied by increased expression of caspase-3.CONCLUSION:rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis.Thus,our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.展开更多
基金Supported by grants from Guangzhou Health Agency (No. 2008-YB-034)Guangdong Department of Science and Technology (No. 83083)
文摘Objective: To evaluate transduction efficiency with recombinant adenovirus-mediated p53 (rAd/p53) therapy in a human colon cancer mouse model by intra-tumoral injection and intra-arterial delivery. Methods: The tumor pieces of human colon cancer SW480 were implanted in the livers of 45 nude mice. These mice were administrated with rAd/p53 by intratumoral injection and intra-arterial delivery. After 24 h, 48 h and 72 h rAd/p53 administration, 5 mice each group were killed with over anesthesia and their livers were removed. P53 expression and apoptosis of tumor and liver were assessed. Results: P53 expression and apoptosis of intratumoral administration group was higher than tail vein group and control group. Apoptosis and p53 expression of livers in three groups had no significant difference. Conclusion: p53 gene transduction efficiency and anticancer effect of rAd/p53 is much better by intra-tumoral injection than intra-arterial delivery.
基金Supported by Xuzhou Science and Technology Development Fund,No. XM07C039
文摘AIM:To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy.METHODS:Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone,oxaliplatin(OXA) alone,or a combination of both.Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay and the expression levels of p53,Bax and Bcl-2 were determined by immunohistochemistry.The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry.RESULTS:Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time-and dosedependent manner;moreover,significant synergistic effects were observed when these treatments were combined.Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone,OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells.Furthermore,flow cytometry showed that rAd-p53 alone,OXA alone or combination treatment induced apoptosis of gastric cancer cells,which was accompanied by increased expression of caspase-3.CONCLUSION:rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis.Thus,our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment.
