Influence of indomethacin and difluoromethylornithine on human tumour growth in nude mice

Abstract

Biopsy material from six human colorectal carcinomas was transplanted to 114 nude mice. A treatment protocol was established which included no treatment (control, C), indomethacin (I), difluoromethylornithine (D) or a combination of both (ID). The influence of the various drugs on tumour weight and protein kinase CK2 activity was monitored. CK2 activity was measured because in all tumours examined so far the enzyme activity was found to be enhanced several-fold when compared to the non-neoplastic tissue of the same patient. More than half of the investigated tumours showed a conspicuous reduction in weight after drug treatment, and I and the combination of D/I were significantly effective using the mixed model analysis. Furthermore, we have tried to discover whether there is a change in the subcellular localisation of protein kinase CK2 subunits associated with drug treatment. We analysed the tumours and the non-neoplastic control tissues by immunohistochemistry using antibodies directed against the CK2 subunits and against the proliferation marker Mib. In addition, we have also investigated the behaviour of the nucleolar protein B23 which has also been shown to be enhanced several-fold in rapidly proliferating tissue and which is also a substrate for CK2. The immunohistochemical data suggest that, irrespective of the drug treatment and the observed reduction in CK2 activity, the CK2 subunits remain localised in the nucleus.