Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

1533 - Glutathione S-transferase M subfamily in TMZ-resistant glioblastoma cells

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Shu Yu Cheng

Citation

Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304

Authors

S.Y. Cheng1, W. Chen2, Z. Wen3

Author affiliations

  • 1 Doctoral Degree Program In Marine Biotechnology, National Sun Yat-sen University, 804 - Kaohsiung/TW
  • 2 Department Of Neurosurgery, Chang Gung Memorial Hospital, 833 - Kaohsiung/TW
  • 3 Department Of Marine Biotechnology And Resources, National Sun Yat-sen University, 804 - Kaohsiung/TW
More

Resources

Abstract 1533

Background

Glioblastoma multiforme (GBM), the most aggressive central nervous system cancer, is highly angiogenetic and infiltrative with high potential of resistance to chemotherapy and radio therapy. The median survival of primary GBM patients is approximately 14.6 months, despite patients receiving aggressive treatment with surgery, radiotherapy, and alkylating chemotherapy drugs such as temozolomide (TMZ). Some research results point out more than 90% of patients show no response after the second cycle of current GBM chemotherapy. Glutathione S-transferase (GST) is an important detoxification protein family that highly correlates with drug inactivation and multidrug resistance.

Methods

In our study, we generated TMZ-resistant glioblastoma GBM8401 cells (GBM8401-TMZ-R) over a 130-day period. We compared TMZ resistance level in TMZ-sensitive cell lines U87MG, A172 and GBM8401 with TMZ-resistant cell lines GBM8401-TMZ-R, T98G and U138 through cell toxicity assays and O-6-Methylguanine-DNA Methyltransferase (MGMT) expression. Moreover, we investigated the mRNA profiles of GBM8401, GBM8401-TMZ-R, and T98G cells by using next generation sequencing (NGS) for analyzing.

Results

We found GBM8401-TMZ-R cells with significantly higher MGMT expression and increased TMZ tolerance. GSTM subfamily proteins, which are located in human chromosome 1, showed different basal expressions in the GBM cell lines we tested. Surprisingly, GBM8401-TMZ-R cells showed higher GST activity and increased GSTM1 and GSTM5 protein levels than GBM8401. GBM8401-TMZ-R cells also displayed higher glycolytic capacity in a Seahorse extracellular flux (XF) analyzer. We also analyzed the expression of GST subfamilies and drug resistance-related genes by NGS.

Conclusions

From these results, we theorized that certain GST proteins may play a key role in TMZ-resistant glioblastoma cells. We hope this study will provide potential therapeutic targets for TMZ-resistant GBM patients.

Clinical trial identification

Legal entity responsible for the study

National Sun Yat-sen University.

Funding

Ministry of Science and Technology, R.O.C (Taiwan).

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.