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

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

doi:10.3892/ijo.12.3.665

Mar 1998 Volume 12 Issue 3

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Mar 1998 Volume 12 Issue 3

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Article

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

Authors:
- J Fueyo
- C Gomez-Manzano
- V K Puduvalli
- P Martin-Duque
- R Perez-Soler
- V A Levin
- W K Yung
- A P Kyritsis
View Affiliations / Copyright

Affiliations: Department of Neuro-Oncology, The University of Texas, M.D. Anderson Cancer Center, Box 316, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
Pages: 665-674
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Published online on: March 1, 1998

https://doi.org/10.3892/ijo.12.3.665
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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 p16-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 p16-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.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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