[Therapeutic effect of ovarian intra-arterial infusion of GE7-delivery system-mediated HSVl-tk/ganciclovir gene therapy in a rat model of malignant ovarian tumor].
OBJECTIVE
To observe the gene expression of herpes simplex virus type 1 thymidine kinase (HSVl-tk) in rat malignant ovarian tumor tissues and the therapeutic effect of ganciclovior (GCV) after intra-arterial infusion of HSVl-tk gene therapy mediated by GE7-delivery system.


METHODS
A GE7-polylysine/pCMV-HSV1-tk/polylysine-HA20 4-element complex was constructed. Eighteen rats with DMBA-induced ovarian tumor were divided into 3 groups as Atk, ANS and Vtk groups. The 4-element complex GE7-polylysine/pCMV-HSV1-tk/polylysine-HA20 was injected via the ovarian artery into the rats of Atk group, saline buffer was injected in the ANS groups, and the 4-element complex was injected via the tail vein into the rats of Vtk group. All rats received intraperitoneal injection of GCV in a dose of 50 mg/kg daily for 10 days. The rats were sacrificed 3 days after the final dose of GCV, and the tumor weight was measured and tumor growth inhibition rate was calculated. Flow cytometry was used to assess the cell cycle and apoptosis.


RESULTS
The tumor weight in the rats of Atk group was (4.77 ± 2.31) g, significantly lower than that of ANS group [(14.66 ± 6.26) g, P < 0.01] and Vtk group [(17.53 ± 7.19) g, P < 0.01]. The tumor growth inhibition rate of the Atk group was 67.5%, while that of Vtk group was -19.6%. The flow cytometry showed that S-phase tumor cells in the Atk group were (54.32 ± 9.65)%, significantly higher than that in the ANS (27.43 ± 9.22)% and (30.16 ± 11.57)% in the Vtk group (both P < 0.01). The tumor cell apoptosis rate in the Atk group was (39.15 ± 12.16)%, significantly higher than that in the ANS group [(11.86 ± 5.28)%, P < 0.01] and Vtk group [(14.32 ± 6.43)%, P < 0.01].


CONCLUSIONS
HSV1-tk/GCV gene therapy system mediated by GE7 non-viral delivery system via ovarian arterial infusion effectively causes cell cycle arrest at S phase and enhances cell apoptosis, therefore, exerts an inhibitory effect on tumor growth.
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
Wei
W
Jiang
Xiao-xia
XX
Liu
Yu
Y
Kang
Zhi-min
ZM
Shao
Wen-jiang
WJ
Zhou
Jian-ren
JR
Gu
Cong-jian
CJ
Xu
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000378:metabolism; D007261:Infusions, Intra-Arterial; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
D000998:Antiviral Agents; D015127:9,10-Dimethyl-1,2-benzanthracene; D013937:Thymidine Kinase; D015774:Ganciclovir