ADENOVIRUS－MEDIATED P53 GENE TRANSFER INCREASES THE THERMOSENSITIVITY OF HUMAN GASTRIC CARCINOM ACELL LINES （IN VITRO AND IN VIVO）

Adenovirus-mediated p53 gene transfer increases the thermosensitivity of human gastric carcinoma cell lines (in vitro andin vivo)

Objective: To investigate the effect of adenovirus-mediated p53 (Adp53) transfer on thermosensitivity of human gastric carcinoma cell lines (BGC823). Methods: Two human gastric carcinoma cell lines with different p53 status, BGC823-wtp53 cell (abbreviate W) bearing the wilt-type p53 and BGC823-mutp53 cell (abbreviate M) bearing the mutant p53, were cultured with DMEM medium and were infected with Adp53 at a viral multiplicity of infection of 100 (1:100MOI) for 48h before heating. Cell cycle redistribution and apoptosis of two human gastric carcinoma cell lines in 24h at 37°C after heat treatment at 42°C for 2h or 43°C for 0.5h were analyzed by flow cytometry. Relative tumor volume growth curves were used in a nude mouse tumor model of the two cell lines following hyperthermia at 43 C for 0.5h after 48h intratumoral injection of 1×108 pfu of Adp53 to evaluate thermoenhancemet effectin vivo. Results:In vitro study showed that both W and M cells infected with Adp53 and treated with heating had strong arrest in G2 (after heating at 42°C for 2h, 34.0% of original population for W cells and 25.3% of original population for M cells) and produced obvious apoptotic response. The apoptosis rate showed 230% increased (for W cells) and 110% increase (for M cells) compared with heating only control.In vivo study showed that the growth of tumor of both W cells and M cells was significantly delayed by hyperthemia combining with Adp53 as compared to tumors receiving either treatment alone. Conclusion: This study demonstrated that Adp53 transfer increased cellular apoptosis and thermo- sensitivityin vitro and tumor thermosensitivityin vivo independent of cellular intrinsic p53 status. These results support the combined used of p53 gene therapy with hyperthermia in clinical trials. Foundation item: This work was supported by the National Natural Foundation of China (No. 39670234 ) Biography: ZHANG Shan-wen(1946–), male, professor, Department of Radiotherapy, Peking University School of Oncology, majors in radiation oncology and gene therapy.