Gene therapy with HSV-TK: a promising tool for pancreatic cancer treatment?

Purpose: Aim of this study was to ascertain whether transduction of the pancreatic cancer cell lines MIAPaCa2, CAPAN1, PANC1 and PSK1 with the HSV-TK gene increases the death rate after GCV treatment. Methods: The vector contained human IL-2 gene and HSV-TK. TK+ cells were selected after 2 weeks G418 treatment (0.5–1.5 mg/ml). The 4 TK– and the 4 TK+ cell lines were treated daily with GCV at the dosages of 0.001, 0.01, 0.1, 1, 10, 20, 100, 200 and 500 ÌM for 15 days. Cell growth was assessed by means of the XTT assay. Results: GCV treatment did not modify TK-cell growth at 20 ÌM or less, while 100 ÌM or more completely inhibited cell growth (cytotoxic dosages). The lowest GCV dosage able to inhibit TK+ cell growth varied in relation to the cell line: 20 ÌM for PSK-1 (p ! 0.05 as compared to the corresponding TK-cell line), 1 ÌM for MIAPaCa2 (p ! 0.05), PANC1 (p ! 0.001) and CAPAN1 cells (p ! 0.001). While PSK1, PANC1 and CAPAN1 TK+ cell growth was completely inhibited after GCV treatment at the adequate dosage, MIAPaCa2 TK+ cell growth was only delayed even when the highest non-toxic GCV dosage (20 ÌM) was used. Conclusions: These data indicate that gene therapy with suicide genes in pancreatic cancer, although promising, needs to be carefully evaluated before any application in clinical practice.