Related Experiment Video
Updated: Jun 10, 2026
Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
Published on: December 30, 2025
TP53 regulates human AlkB homologue 2 expression in glioma resistance to Photofrin-mediated photodynamic therapy
1Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region, China.
Background:
Photodynamic therapy (PDT) is a promising adjuvant therapy in cancer treatment. However, cancers resistant to PDT, mediated through the efflux of photosensitisers by means of P-glycoprotein or ATP-binding cassette transporter proteins, have been reported. The DNA repair has also been suggested to be responsible for PDT resistance, but little is known about the repair pathways and mechanisms involved. Therefore, this study aimed to investigate the possible function of six major DNA repair mechanisms in glioma cells resistant to Photofrin-mediated PDT (Ph-PDT).
Methods:
The U87 glioma cells relatively resistant to Ph-PDT were obtained by recovering the viable cells 3 h after PDT treatment. The mRNA and protein expression levels of DNA repair genes were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and western blotting, respectively. Small-interfering RNA and chromatin-immunoprecipitation assays were used to further examine the relationship between AlkB, an alkylation repair homologue 2 (Escherichia coli) (ALKBH2) and Ph-PDT responsiveness, and transcription factors involved in ALKBH2 transcription.
Results:
The ALKBH2 of DNA damage reversal was significantly increased at both mRNA and protein levels from 30 min to 48 h post-treatment with Ph-PDT. Conversely, down-regulating ALKBH2 expression enhances Ph-PDT efficiency. Furthermore, our data clearly show for the first time that tumour protein (TP53) is directly involved by binding to the promoter of ALKBH2 in mediating Ph-PDT resistance.
Conclusion:
C The DNA damage reversal mechanisms may have important functions in Ph-PDT resistance through the activation of ALKBH2 by TP53.
Insights
This study reveals that increased DNA repair via ALKBH2, activated by TP53, drives resistance to photodynamic therapy (PDT) in glioma cells. Targeting this pathway could improve PDT efficacy for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Photodynamic therapy (PDT) shows promise as an adjuvant cancer treatment.
- Cancer resistance to PDT can be mediated by photosensitizer efflux or DNA repair mechanisms.
- The specific DNA repair pathways involved in PDT resistance remain largely uncharacterized.
Purpose of the Study:
- To investigate the role of six major DNA repair mechanisms in glioma cells exhibiting resistance to Photofrin-mediated PDT (Ph-PDT).
Main Methods:
- U87 glioma cells with relative Ph-PDT resistance were established.
- Quantitative real-time RT-PCR and western blotting assessed DNA repair gene expression.
- Small-interfering RNA and ChIP assays explored the ALKBH2-Ph-PDT responsiveness link and its transcriptional regulation.
Main Results:
- AlkB, an alkylation repair homologue 2 (Escherichia coli) (ALKBH2) expression significantly increased post-Ph-PDT at mRNA and protein levels.
- Down-regulating ALKBH2 enhanced Ph-PDT efficiency, indicating its role in resistance.
- Tumor protein 53 (TP53) was identified as a direct transcriptional activator of ALKBH2, mediating Ph-PDT resistance.
Conclusions:
- DNA damage reversal mechanisms, particularly ALKBH2, play a crucial role in Ph-PDT resistance.
- TP53 activation of ALKBH2 is a key pathway conferring Ph-PDT resistance in glioma.
- Targeting the TP53-ALKBH2 axis may represent a strategy to overcome Ph-PDT resistance.
Related Concept Videos
02:23Abnormal Proliferation
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:23Negative Regulator Molecules