[Studies on herpes simplex virus thymidine kinase gene and GCV system for treatment of human bladder carcinoma]

To investigate the antitumor effect of herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system on human bladder cancer cells (T24), a retroviral vector with the gene (pLXSN-TK) was transduced into the packaging cell line PA317. A nude mouse model with human T24 was established to examine the in vivo efficacy. The animals were randomly assigned to two treatment groups and two control groups. Treatment I and Treatment II were given in situ injection of virus suspension and PA317/TK respectively, followed by treatment with GCV for 14 days. Control I and Control II were given in situ injection of same volume of normal saline and PA317/TK respectively, followed by treatment with GCV and with normaly physiologic saline respectively for 14 days. The weight and the volume of tumor were measured. HSV-TK mRNA expression was determined by hybridization in situ. Cell apoptosis was evaluated by flow cytometry (FCM) and termininal deoxynucleofidyl transferase-mediated dUTP nick end labelling (TUNEL) technique. The results showed: (1) In vivo, the retrovirus transferred HSV-TK gene can be transduced into human bladder cancer cell T24. The tumors in T24 mice with TK gene transduced were much smaller than those in other groups. (2) After treatment with HSV-TK/GCV, the phenomenon of bladder ceancer cell apoptosis was more conspicuous as compared with that of other groups. Therefore, HSV-TK/GCV system can suppress the growth of T24 in vivo and may relate to "bystander effect". It could be a valuable therapy for human bladder cancer.