Anti-tumour effects by a trimodal combination of temozolomide, meloxicam and X-rays in cultures of human glioma cells.
OBJECTIVE
To investigate the possible cytotoxic interactions between the chemotherapeutic drug temozolomide (TMZ) and the cyclooxygenase-2 inhibitor meloxicam (MLC) or of both drugs combined with X-rays in three human glioma cell lines (D384, Hs 683 and U251).


METHODS
Cells were exposed to TMZ (96 hours) and MLC was co-incubated during the last 24 h. Thereafter, cells were irradiated with X-rays and plated for a clonogenic assay. Total cell numbers and the numbers of surviving cells were determined to study the recovery of the cell populations (up until 19 days) following different combinations of TMZ, MLC and X-rays.


RESULTS
The combination of MLC and TMZ caused an enhanced cytotoxic effect in D384 and Hs 683. Various treatment combinations demonstrated significant radiation enhancement in all three cell lines. Long-term observations of D384 cells demonstrated that the repopulation rates of the surviving cells are far less affected by the various treatment protocols than those from the non-surviving cells.


CONCLUSIONS
The present study demonstrates that a combination of TMZ and MLC resulted in a significant potentiation of their cytotoxicity in D384 and Hs683. The combination of these two drugs can also cause considerable enhancement of the radiation response in human glioma cell lines, although only D384 cells benefit from trimodal over bimodal treatment.
Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands. ka.vannifterik@vumc.nl
Krista A
KA
van Nifterik
Jaap
J
Van Den Berg
Ben J
BJ
Slotman
Johannes
J
Van Rijn
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D003131:Combined Modality Therapy / Q000379:methods; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D000077239:Meloxicam; D000077204:Temozolomide; D013843:Thiazines / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014965:X-Rays
D018906:Antineoplastic Agents, Alkylating; D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D003606:Dacarbazine; D000077239:Meloxicam; D000077204:Temozolomide