Establishment of a Novel Temozolomide Resistant Subline of Glioblastoma Multiforme Cells and Comparative Transcriptome Analysis With Parental Cells

Hai-Anh Ha; Jai-Sing Yang; Fuu-Jen Tsai; Chang-Wei Li; Yih-Dih Cheng; Jianyong Li; Mann-Jen Hour; Yu-Jen Chiu

doi:10.21873/anticanres.15008

Establishment of a Novel Temozolomide Resistant Subline of Glioblastoma Multiforme Cells and Comparative Transcriptome Analysis With Parental Cells

Anticancer Res. 2021 May;41(5):2333-2347. doi: 10.21873/anticanres.15008.

Authors

Hai-Anh Ha^{1

2}, Jai-Sing Yang³, Fuu-Jen Tsai^{4

5

6}, Chang-Wei Li⁷, Yih-Dih Cheng¹, Jianyong Li⁸, Mann-Jen Hour⁹, Yu-Jen Chiu^{10

11

12}

Affiliations

¹ School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
² Faculty of Pharmacy, Duy Tan University, Da Nang, Vietnam.
³ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan, R.O.C.
⁴ Human Genetics Center, Department of Medical Research, Taichung, Taiwan, R.O.C.
⁵ Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan, R.O.C.
⁶ School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
⁷ Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, R.O.C.
⁸ Army Medical University (The Third Military Medical University), Chongqing, P.R. China.
⁹ School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.; [email protected] [email protected].
¹⁰ Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.; [email protected] [email protected].
¹¹ Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, R.O.C.
¹² Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, R.O.C.

PMID: 33952458
DOI: 10.21873/anticanres.15008

Abstract

Background/aim: Glioblastoma multiforme (GBM) is a lethal disease with a high rate of chemoresistance to temozolomide (TMZ). The aim of the study was to establish a TMZ-resistant subline from the GBM-8401 cell line to determine the mechanisms of resistance and identify novel effective therapeutics for TMZ-resistant GBM.

Materials and methods: Comparative transcriptome analysis of GBM-8401/TMZR cells and the parental line was performed using Ion Torrent sequencing. Differentially expressed genes (DEGs) between the GBM-8401/TMZR and GBM-8401 cell lines were analyzed.

Results: Transcriptomic profiling of GBM-8401/TMZR cells revealed DEGs involved in the retinoblastoma (RB) signaling, DNA damage response (DDR) pathway, and DNA repair mechanisms.

Conclusion: In vitro and in vivo cell-based GBM models should be used in further biomedical studies to investigate the underlying mechanisms of TMZ-resistant GBM.

Keywords: GBM-8401/TMZR; Glioblastoma multiforme; MGMT-mediated DNA repair; TMZ resistance; mismatch repair; temozolomide (TMZ).

Publication types

Comparative Study

MeSH terms

Antineoplastic Agents, Alkylating / pharmacology
Cell Line, Tumor
Cell Survival / drug effects
Cell Survival / genetics
DNA Damage
DNA Repair / genetics
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm / genetics*
Gene Expression Profiling / methods*
Gene Expression Regulation, Neoplastic / drug effects*
Glioblastoma / genetics*
Glioblastoma / pathology
Humans
Models, Genetic
Retinoblastoma Protein / genetics
Signal Transduction / genetics
Temozolomide / pharmacology*

Substances

Antineoplastic Agents, Alkylating
Retinoblastoma Protein
Temozolomide