RRC ID 64619
著者 Kunishige I, Samejima Y, Shiki Y, Moriyama A, Meruelo D, Saji F, Murata Y.
タイトル Suicide gene therapy for human uterine adenocarcinoma cells using herpes simplex virus thymidine kinase.
ジャーナル Gynecol Oncol
Abstract In gene therapy, the herpes simplex virus thymidine kinase (HSV-tk) gene is widely used as a suicide agent. Tumor cells expressing HSV-tk are sensitive to nucleoside analogs such as ganciclovir (GCV). An advantage of this system is the bystander killing effect whereby HSV-tk-positive cells exposed to GCV are lethal to surrounding HSV-tk-negative cells. We transfected the HSV-tk gene into a human cervical adenocarcinoma cell line, BU25TK-, and a human endometrial adenocarcinoma cell line, HHUA, by the Lipofectine method. The sensitivity of HSV-tk-positive cells to GCV and bystander killing effect on HSV-tk-negative cells were examined in vitro. HSV-tk-positive cells were sensitive to GCV at concentrations of 1 to 100 microg/ml in a dose- and time-dependent manner. The growth of HSV-tk-negative cells was inhibited when the population of cultured cells contained more than about 3% HSV-tk-positive cells. Moreover, for BU25TK- cells, HSV-tk-positive cells were injected into SCID mice subcutaneously and the effects of GCV therapy and bystander killing at a daily concentration of 25 mg/kg for 14 days were examined. HSV-tk-positive tumors transduced into SCID mice almost disappeared upon GCV treatment. Furthermore, tumor reduction was observed when mixtures of HSV-tk-negative cells containing more than 20% HSV-tk-positive cells were injected into SCID mice. In conclusion, the HSV-tk/GCV system might be applied to both cervical and endometrial adenocarcinoma.
巻・号 72(1)
ページ 16-25
公開日 1999-1-1
DOI 10.1006/gyno.1998.5224
PII S0090-8258(98)95224-6
PMID 9889024
MeSH Adenocarcinoma / genetics Adenocarcinoma / therapy* Animals Female Ganciclovir / therapeutic use Genetic Therapy / methods* Humans Mice Mice, SCID Simplexvirus* / genetics Thymidine Kinase* / genetics Tumor Cells, Cultured Uterine Neoplasms / genetics Uterine Neoplasms / therapy*
IF 4.623
リソース情報
ヒト・動物細胞 HHUA(RCB0658)