Inhibitory Effect Of Oncolytic Adenovirus H101 On Human Malignant Glioma Cells SHG-44 And Its Transplanted Models In Nude Mice

Objective: Malignant gliomas are the most frequently occurring primary brain tumors and are resistant to conventional therapy. Current therapy is surgery excision and treatment such as radiation and chemotherapy after operation. Because of unclear boundary, it could not be excised completely. And it would recurrence in 8 months, no wonder the median survival time rarely exceeds 1 year. Despite recent progress in radiotherapy, chemotherapy,and surgical techniques,the survival of patients with glioma has not improved significantly during the past 2 decades.To conquer these malignant tumors,various new therapies have been under development, including gene therapies using adenoviral vectors. Conditionally replicative adenoviruses H101 are designed to have a limited ability to replicate themselves in the targeted tumor cells but not in other normal tissues. Tumor cell killing is achieved not by the genes delivered by the vectors but by the oncolysis induced by the replicated viruses through their original nature as adenoviruses. Amplified viral vectors also spread to the adjacent tumor cells and kill these cells in the same manner. This type 5 adenovirus has an 800-bp deletion in the E1B region encoding the 55 kD protein in infected cells, which binds and inactivates cellular p53.Therefore the adenovirus is thought to replicate efficiently and cause cytopathic effects in tumor cells that lacking functional p53, which could't replicate in p53 positive normal cells and finally disseminate virus particles to infect other tumor cells. The clinical trials currently undergoing for the treatment of head and neck cancers and other cancers with apparently promising results.in this study we aimed to evaluate the atitumor effect of H101 on human malignant glioma cells SHG-44 and its transplanted models in nude mice.Methods: The cytotoxicities of H101 were deceted by CPE and MTT assay in virtro. Xenograft model in nude mouse was used to determine the aititumor effect in vivo.and the expression of the virus hexon protein were detected by immunohistochemistry and RT-PCR to evaluate the propagation of H101 in tumor tissue.Results: In vitro,H101 inhibited the growth of SHG-44 cells,the cell viability repression rates were 46.5%,53%,64.6%,69.3%,72.4%and 80.4% respectively,while SHG-44 cells treated with H101 alone at 10~4vp , 10~5vp, 10~6vp, 10~7vp, 10~8 vp, 10~9 vp.H101 effectively inhibited the growth of tumor xenografts in vivo, which inhibit ration rate were 47.4%.Virus replication was detected on a large scale in tumor tissue treated with H101 by RT-PCR and immunohistochemistry.Conclusions: H101 can inhibit distinctly the growth of SHG-44 cell in vitro and in vivo...