High-level transgene expression mediated by the piggyBac transposon enhances transgenic therapeutic effects in cervical cancer xenografts.
The piggyBac (PB) transposon is a recently identified, active and flexible transgene vector, combining the advantages of non-viral gene delivery with genomic integration and persistent transgene expression. In this study, we utilized the PB transposon to carry the herpes simplex thymidine kinase (HSV-tk) and red fluorescent protein (mRFP1) reporter genes into the HeLa cervical cancer cell line or tumor xenografts of cervical cancer. Our data showed that HSV-tk and mRFP1 were expressed in HeLa cells and tumor xenografts three weeks after intratumoral injection. The mRNA and protein levels of HSV-tk and mRFP1 were increased by using the PB transposon vector. Our system also demonstrated that sensitivity of transfected HeLa cells to the pro-drug ganciclovir (GCV) was enhanced in vitro and in vivo. Furthermore, our data indicated that the enhanced transgenic therapeutic effect was strongly associated with high-level transgene expression mediated by the PB transposon. Our results suggest that applying the PB transposon in HSV-tk gene delivery and GCV treatment is a promising gene therapy strategy in the treatment of cervical cancer.
Kang
Yu
Y
Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
Yu
Wenbo
W
Sun
Qinwen
Q
Zhang
Xiaoyan
X
Jiang
Wei
W
Wu
Chaoqun
C
Chen
Chunmei
C
Gu
Jianren
J
Zheng
Yufang
Y
Xu
Congjian
C
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002469:Cell Separation; D004251:DNA Transposable Elements / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D011355:Prodrugs / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000235:genetics*; D019076:Transgenes; D002583:Uterine Cervical Neoplasms / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays; D000097573:Red Fluorescent Protein
D000970:Antineoplastic Agents; D004251:DNA Transposable Elements; D015774:Ganciclovir; D008164:Luminescent Proteins; D011355:Prodrugs; D013937:Thymidine Kinase; D000097573:Red Fluorescent Protein