Combined effect of 2-5A-linked antisense against telomerase RNA and conventional therapies on human malignant glioma cells in vitro and in vivo

  • Authors:
    • Eiji Iwado
    • Shigeru Daido
    • Yasuko Kondo
    • Seiji Kondo
  • View Affiliations

  • Published online on: November 1, 2007     https://doi.org/10.3892/ijo.31.5.1087
  • Pages: 1087-1095
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Abstract

We recently showed that therapy with 2'-5'-oligoadenylate (2-5A)-linked antisense against human telomerase RNA component (2-5A-anti-hTR) is a novel telomerase-targeting strategy against malignant gliomas. In this study, we investigated conventional chemotherapeutic agents and γ-irradiation (IR) to determine whether they could augment the efficacy of 2-5A-anti-hTR against these tumors in vitro and in vivo. Treatment with 2-5A-anti-hTR inhibited the viability of U373-MG and U87-MG malignant glioma cells in a dose-dependent manner; the antitumor effect resulted from induction of apoptosis. Also, telomerase-positive astrocytes with oncogenic Ras were more sensitive to 2-5A-anti-hTR than were those without oncogenic Ras. In addition, we sought to determine the combined effect of 2-5A-anti-hTR with N, N'-bis (2-chloroethyl)-N-nitrosourea (BCNU), cisplatin (CDDP), paclitaxel (PTX), temozolomide (TMZ), or IR. When we administered the combination treatments on the same day, PTX and IR showed a greater combined effect with 2-5A-anti-hTR on both tumor cell lines than did BCNU, CDDP and TMZ. However, all of the combination regimens were synergistic when we first treated tumor cells with 2-5A-anti-hTR for 24 h and then exposed them to the conventional treatments. Apoptosis-inducing agents (CDDP and PTX) but not autophagy-inducing therapies (TMZ and IR) enhanced the incidence of apoptosis caused by 2-5A-anti-hTR. Lastly, we observed a combinatorial effect of 2-5A-anti-hTR and TMZ in vivo in subcutaneous U87-MG tumors in nude mice. Interestingly, treatment with TMZ increased the incidence of apoptosis in subcutaneous tumor cells treated with 2-5A-anti-hTR. These results suggest that 2-5A-anti-hTR is preferable in combination with established cancer therapies.

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November 2007
Volume 31 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Iwado, E., Daido, S., Kondo, Y., & Kondo, S. (2007). Combined effect of 2-5A-linked antisense against telomerase RNA and conventional therapies on human malignant glioma cells in vitro and in vivo. International Journal of Oncology, 31, 1087-1095. https://doi.org/10.3892/ijo.31.5.1087
MLA
Iwado, E., Daido, S., Kondo, Y., Kondo, S."Combined effect of 2-5A-linked antisense against telomerase RNA and conventional therapies on human malignant glioma cells in vitro and in vivo". International Journal of Oncology 31.5 (2007): 1087-1095.
Chicago
Iwado, E., Daido, S., Kondo, Y., Kondo, S."Combined effect of 2-5A-linked antisense against telomerase RNA and conventional therapies on human malignant glioma cells in vitro and in vivo". International Journal of Oncology 31, no. 5 (2007): 1087-1095. https://doi.org/10.3892/ijo.31.5.1087