CDT6-expression can alter tumor sensitivity to chemotherapy.
BACKGROUND
Cornea-derived transcript 6 (CDT6 = AngX) has been shown to have an anti-tumor effect.


METHODS
We transfected the murine melanoma cell line B16-F10 with the CDT6 gene and compared the sensitivity to cytostatic drugs of the resulting cell line, B16-CDT6, to that of the empty vector-transfected control cell line B16-CMV.


RESULTS
The B16-CDT6 line showed a significantly increased sensitivity to doxorubicin as well as a tendency towards a decreased sensitivity to cisplatin. To further resolve the mechanism of the increase in sensitivity to doxorubicin, we also tested the cytotoxic agents vincristine, etoposide and taxol. However no difference in sensitivity for these drugs was found between the B16-CDT6 and the control cell line.


CONCLUSIONS
CDT6 increased the sensitivity to doxorubicin in a mechanism probably not related to interference with the efflux pumps MRP, Pgp or the DNA-associated target enzyme topoisomerase II. Altered gene expression induced by gene therapy might influence tumor sensitivity to chemotherapy.
Bouïs
Diane
D
Department of Medical Oncology, University Hospital Groningen, P.O. Box 30001, 9700RB Groningen, The Netherlands.
Hospers
Geke A P
GA
Meijer
Coby
C
Dam
Wendy
W
Mulder
Nanno H
NH
D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D003001:Cloning, Molecular; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology; D014162:Transfection; D014750:Vincristine / Q000494:pharmacology
D043925:Angiogenesis Inducing Agents; D000970:Antineoplastic Agents; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin