[Experimental studies on human lung cancer gene-therapy with HSV-TK/GCV system]

Evaluate the clinical potential of HSV-TK/GCV system in gene-therapy of tumors by using this system to treat human lung cancer A549 cells in vitro and in vivo.

The in vitro sensitivity levels of A549/TK (TK-tranfered A549) cells and wild type A549 cells to GCV were expressed as IC50 which was measured with MTT assay after treating both cells for 72 hrs. In vivo study, The nude mice bearing A549/TK tumor or A549 tumor were used as experimental models. All the animals were divided into 3 groups. Group 1, the animals bearing A549/TK tumor would be treated with GCV. Group 2, The animals bearing A549/TK tumor would be treated with saline. Group 3, The animals bearing A549 tumor would be treated with GCV. When the tumors reached to 200-300 mg the animals would be injected intraperitoneally with GCV solution (100 mg.kg-1.day-1) or equal volume of saline for two weeks. In this period and the following four weeks, the tumor weights were measured and calculated with the experience formula once every three or four days.

In vitro study showed that the A549/TK cells were apparently killed in a 20 mumol/L GCV solution while the wild type A549 cells grew normally under the same condition. The IC50 of A549/TK cells in GCV solution was 0.5 mumol/L and that of A549 cells 500 mumol/L, showing a 1,000 fold difference (P < 0.01). In vivo experiment GCV had compelled the A549/TK tumors to lead to a regression of 92%, meanwhile the A549 tumors treated with GCV increased 3.9 times in weight in the first seventeen days of experiment. Group 2 tumors A549/TK tumors which were treated with saline, grew as well as group 3 did. There was a significant difference (P < 0.01) between group 1 and other groups.

GCV could specifically and effectively kill the TK-transfered A549 cells in vitro and in vivo. This result suggested that the HSV-TK/GCV system may have a clinical potential for gene therapy of lung cancer.