ONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them. To date, clinical trials of this adenovirus have demonstrated marked safety but not potent...ONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them. To date, clinical trials of this adenovirus have demonstrated marked safety but not potent enough when it was used alone. In this paper, we put forward a novel concept of Gene-ViroTherapy strategy and in this way, we constructed an armed therapeutic oncolytic adenovirus system, ZD55-gene, which is not only deleted of ElB 55-kD gene similar to ONYX-015, but also armed with foreign antitumor gene. ZD55-gene exhibited similar cytopathic effects and replication kinetics to that of ONYX-015 in vitro. Importantly, the carried gene is expressed and the expression level can increase with the replication of virus. Consequently, a significant antitumoral efficacy was observed when ZD55-CD/5-FU was used as an example in nude mice with subcutaneous human SW620 colon cancer. Our data demonstrated that ZD55-gene, which utilizing the Gene-ViroTherapy strategy, is more efficacious than each individual component in vivo.展开更多
联合运用NF-κB小分子抑制剂小白菊内酯(parthenolide,PTL)和携带TRAIL的溶瘤腺病毒ZD55-TRAIL在体外杀伤人肝癌细胞株Hep3B,以评估两者联用的实验疗效。首先用Adeasy系统包装ZD55-TRAIL病毒;分别用MTT、结晶紫和Hoechst33342荧光染色...联合运用NF-κB小分子抑制剂小白菊内酯(parthenolide,PTL)和携带TRAIL的溶瘤腺病毒ZD55-TRAIL在体外杀伤人肝癌细胞株Hep3B,以评估两者联用的实验疗效。首先用Adeasy系统包装ZD55-TRAIL病毒;分别用MTT、结晶紫和Hoechst33342荧光染色实验检测ZD55-TRAIL、ZD55-TRAIL和PTL联合运用对肝癌细胞株Hep3B和正常肝细胞QSG-7701的增殖抑制作用。结果表明:10 MOI ZD55-TRAIL联合PTL处理72 h后,Hep3B细胞的存活率仅为44%,但对QSG-7701细胞无明显损伤;而10 MOI的ZD55-TRAIL和PTL分别单独处理后细胞存活率为70%和66%;结晶紫实验及Hoechst33342染色结果表明联合处理组的Hep3B细胞凋亡特征更加明显。溶瘤腺病毒ZD55-TRAIL联合PTL在体外对肝癌细胞Hep3B具有显著的杀伤性,而对QSG-7701细胞无明显毒副作用。展开更多
基金supported by the Key Project of the Chinese Academy of Sciences(No.KSCX2-3-06)the National Natural Science Foundation of China(No.30120160823)the Chinese National“863”High Tech Project Foundation grant(No.2002AA216021).
文摘ONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them. To date, clinical trials of this adenovirus have demonstrated marked safety but not potent enough when it was used alone. In this paper, we put forward a novel concept of Gene-ViroTherapy strategy and in this way, we constructed an armed therapeutic oncolytic adenovirus system, ZD55-gene, which is not only deleted of ElB 55-kD gene similar to ONYX-015, but also armed with foreign antitumor gene. ZD55-gene exhibited similar cytopathic effects and replication kinetics to that of ONYX-015 in vitro. Importantly, the carried gene is expressed and the expression level can increase with the replication of virus. Consequently, a significant antitumoral efficacy was observed when ZD55-CD/5-FU was used as an example in nude mice with subcutaneous human SW620 colon cancer. Our data demonstrated that ZD55-gene, which utilizing the Gene-ViroTherapy strategy, is more efficacious than each individual component in vivo.
文摘联合运用NF-κB小分子抑制剂小白菊内酯(parthenolide,PTL)和携带TRAIL的溶瘤腺病毒ZD55-TRAIL在体外杀伤人肝癌细胞株Hep3B,以评估两者联用的实验疗效。首先用Adeasy系统包装ZD55-TRAIL病毒;分别用MTT、结晶紫和Hoechst33342荧光染色实验检测ZD55-TRAIL、ZD55-TRAIL和PTL联合运用对肝癌细胞株Hep3B和正常肝细胞QSG-7701的增殖抑制作用。结果表明:10 MOI ZD55-TRAIL联合PTL处理72 h后,Hep3B细胞的存活率仅为44%,但对QSG-7701细胞无明显损伤;而10 MOI的ZD55-TRAIL和PTL分别单独处理后细胞存活率为70%和66%;结晶紫实验及Hoechst33342染色结果表明联合处理组的Hep3B细胞凋亡特征更加明显。溶瘤腺病毒ZD55-TRAIL联合PTL在体外对肝癌细胞Hep3B具有显著的杀伤性,而对QSG-7701细胞无明显毒副作用。
