Jul, 2004
Combination of caspase transfer using the human telomerase reverse transcriptase promoter and conventional therapies for malignant glioma cells
INTERNATIONAL JOURNAL OF ONCOLOGY
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- Volume
- 25
- Number
- 1
- First page
- 57
- Last page
- 63
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.3892/ijo.25.1.57
- Publisher
- PROFESSOR D A SPANDIDOS
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 gamma-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 IC75 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.
- Link information
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- DOI
- https://doi.org/10.3892/ijo.25.1.57
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/15201989
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000222162400006&DestApp=WOS_CPL
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=18044382167&origin=inward
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=18044382167&origin=inward
- ID information
-
- DOI : 10.3892/ijo.25.1.57
- ISSN : 1019-6439
- Pubmed ID : 15201989
- SCOPUS ID : 18044382167
- Web of Science ID : WOS:000222162400006