Inhibition of human lung adenocarcinoma growth using survivint34a by low-dose systematic administration.
Anti-apoptosis plays an important role in tumour formation and development. Survivin is a member of the inhibitor of apoptosis (IAP) family, which is a target for anti-cancer drug exploitation was replaced as development. We investigated the role of the homo dominant-negative mutant Survivin-T34A in suppressing human lung adenocarcinomas (A549). The anti-tumour activity of HSurvivinT34A plasmid was evaluated in the A549 cell line and nude mice bearing A549 subcutaneous tumours. Low-dose systemic administration was continuously used. The HSurvivinT34A plasmid (5 meu g/one) complexed with a cationic liposome (DOTAP/Chol) significantly inhibited tumour growth in our model. We observed microvessel density degradation by CD31 immunohistochemistry and apoptotic cell increase by TUNEL assay, PI staining and flow cytometric analysis in the treated group. The present findings suggest that the HSurvivinT34A plasmid complexed with a cationic liposome may provide an effective approach to inhibit the growth of human lung adenocarcinomas in vitro and in vivo.
Shan
Yan
Y
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Chengdu, Sichuan, 610041, China.
Wang
Chunting
C
Yang
Li
L
Chen
Li Juan
LJ
Deng
Hong Xin
HX
Yang
Han Shuo
HS
Li
Zhimian
Z
Li
Zhiyong
Z
Pan
Li
L
Leng
Fei
F
Wei
Yuquan
Y
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009368:Neoplasm Transplantation; D010957:Plasmids; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin