Combination of caspase transfer using the human telomerase reverse transcriptase promoter and conventional therapies for malignant glioma cells
In: International journal of oncology, Jg. 25 (2004), Heft 1, S. 57-63
academicJournal
- print, 39 ref
Zugriff:
Recently, we have reported the therapeutic efficacy of delivering initiator caspase (caspase-8) or executioner active caspase (rev-caspase-6) to telomerase-positive malignant glioma cells using the human telomerase reverse transcriptase (hTERT) gene promoter system (hTERT/caspase-8 or hTERT/rev-caspase-6). In the present study, we investigated if conventional treatments for malignant gliomas augment the efficacy of the hTERT/caspase therapy. First, we demonstrated that hTERT/rev-caspase-6 exhibited a greater ability to induce apoptosis in malignant glioma U87-MG and U373-MG cells than hTERT/caspase-8. Next, as conventional treatments to combine with hTERT/rev-caspase-6, apoptosis-inducing agents [cisplatin (CDDP), paclitaxel (PTX), and BCNU] and non-apoptosis-inducing therapies [temozolomide (TMZ) and γ-irradiation (IR)] were used. Combination of hTERT/rev-caspase-6 gene therapy with PTX yielded a dose-dependent additive effect, while CDDP and BCNU had additive effect only when tumor cells were treated at ICES of each agent. A decline in the combination effect of CDDP and BCNU at IC50 was due to decreased activity of telomerase in treated tumor cells prior to the hTERT/rev-caspase-6 transfer. On the other hand, TMZ or IR had no significant additive effect on induction of apoptosis. These results suggest that agents, which induce apoptosis without inhibiting telomerase activity are a promising counterpart to combine with hTERT/rev-caspase-6 therapy for the management of malignant gliomas.
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Combination of caspase transfer using the human telomerase reverse transcriptase promoter and conventional therapies for malignant glioma cells
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Autor/in / Beteiligte Person: | TAKEUCHI, Hayato ; KANZAWA, Takao ; KONDO, Yasuko ; KOMATA, Tadashi ; HIROHATA, Satoshi ; KYO, Satoru ; KONDO, Seiji |
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Zeitschrift: | International journal of oncology, Jg. 25 (2004), Heft 1, S. 57-63 |
Veröffentlichung: | Athens: Editorial Academy of the International Journal of Oncology, 2004 |
Medientyp: | academicJournal |
Umfang: | print, 39 ref |
ISSN: | 1019-6439 (print) |
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