In vivo cryochemotherapy of a human lung cancer model

Cryotherapy, an efficient technique to destroy tumour cells, is sometimes applied locally as a palliative treatment in lung cancers. It can be performed in combination with chemotherapy. Our aims were to determine in vivo: (1) the effects of cryochemotherapy in a human lung adenocarcinoma, (2) if it presents a benefit compared to the separate treatments and (3) if cryotherapy allows a tumour retention of the drug. Cells from the A549 cell line were xenografted into SCID mice. Tumours were treated by cryotherapy, chemotherapy (injection of Vinorelbine: Navelbine) or both and were studied morphologically at variable time points. Apoptosis was analysed by immunohistochemical staining of cleaved caspase-3 and by TUNEL. Intratumour Navelbine concentration was assessed by high performance liquid chromatography. Necrosis was important 2 h after cryochemotherapy (45% of the tumour surface) and at the later time points. Expression of cleaved caspase-3 was not significantly different from that of untreated tumours, except at the time point of 2 h where it was maximal (58%). Navelbine concentration was more important in tumours treated by chemotherapy than in tumours treated by cryochemotherapy, demonstrating that in our model, the benefit of the association observed 2 h after treatment was not due to a concentration-dependent effect.