Adenovirus-mediated p16 transfer to glioma cells induces G1 arrest and protects from paclitaxel and topotecan: Implications for therapy

J. Fueyo, C. Gomez-Manzano, V. K. Puduvalli, P. Martin-Duque, R. Perez-Soler, V. A. Levin, W. K.A. Yung, A. P. Kyritsis

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Malignant gliomas are highly resistant to chemotherapy, in part because of the blood-brain barrier, which restricts the delivery of chemotherapy to certain areas of tumor and their cellular heterogeneity, which leads to the selection and propagation of resistant clones. However, the molecular basis of the drug resistance is poorly understood. In this study, we examined the effect of the cell cycle-inhibitory protein p16 on the chemosensitivity of human glioma cells. Treatment of the pl6-null glioma cells, U-251 MG and D-54 MG, with paclitaxel and topotecan, resulted in cell death within 4 days. However, overexpression of exogenous wild-type p16 protein using an adenovirus vector resulted in G1, arrest of glioma cells and resistance to the anticancer effect of paclitaxel or topotecan. Specifically, the pl6-expressing cells showed a 30-fold increase in the ID50 of topotecan and a more than 40-fold increase in the ID50 of paclitaxel. These observations indicate that overexpression of molecules that control cell-cycle progression may be partially responsible for causing the resistance of glioma cells to cytocidal drugs.

Original languageEnglish (US)
Pages (from-to)665-669
Number of pages5
JournalInternational journal of oncology
Volume12
Issue number3
Publication statusPublished - Mar 1 1998
Externally publishedYes

    Fingerprint

Keywords

  • Glioma
  • Paclitaxel
  • Topotecan
  • Tumor suppressor genes
  • p16

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fueyo, J., Gomez-Manzano, C., Puduvalli, V. K., Martin-Duque, P., Perez-Soler, R., Levin, V. A., ... Kyritsis, A. P. (1998). Adenovirus-mediated p16 transfer to glioma cells induces G1 arrest and protects from paclitaxel and topotecan: Implications for therapy. International journal of oncology, 12(3), 665-669.