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In vitro induction of PDT resistance in HT29, HT1376 and SK-N-MC cells by various photosensitizers
G Singh1, M Espiritu, X Y Shen
1Hamilton Regional Cancer Center, 699 Concession Street, Hamilton, Ontario, Canada L8V 5C2. gurmit.singh@hrcc.on.ca
Abstract:
Our approach to examine the mechanism(s) of action for photodynamic therapy (PDT) has been via the generation of PDT-resistant cell lines. In this study we used three human cell lines, namely, human colon adenocarcinoma (HT29), human bladder carcinoma and human neuroblastoma. The three photosensitizers used were Photofrin, Nile Blue A and aluminum phthalocyanine tetrasulfonate. The protocol for inducing resistance consisted of repeated in vitro photodynamic treatments with a photosensitizer to the 1-10%-survival level followed by regrowth of single surviving colonies. Varying degrees of resistance were observed. The three induced variants of the HT29 cell line were the most extensively studied. Their ratios of increased survival at the LD90 level range between 1.5- and 2.62-fold more resistant.
Insights
Researchers developed photodynamic therapy (PDT)-resistant cancer cell lines to study PDT mechanisms. HT29 cells showed 1.5- to 2.62-fold increased resistance, aiding in understanding PDT action.
Area of Science:
- Oncology
- Photodynamic Therapy Research
- Cell Biology
Background:
- Photodynamic therapy (PDT) is a cancer treatment modality.
- Understanding the mechanisms of PDT resistance is crucial for improving treatment efficacy.
- Development of PDT-resistant cell lines is a key strategy to investigate resistance mechanisms.
Purpose of the Study:
- To generate and characterize human cancer cell lines resistant to photodynamic therapy (PDT).
- To investigate the differential resistance levels induced by various photosensitizers.
- To establish a model system for studying the molecular mechanisms underlying PDT resistance.
Main Methods:
- Generation of PDT-resistant cell lines using three human cancer cell lines: HT29 (colon adenocarcinoma), bladder carcinoma, and neuroblastoma.
- Treatment with three photosensitizers: Photofrin, Nile Blue A, and aluminum phthalocyanine tetrasulfonate.
- Induction of resistance through repeated in vitro PDT treatments to a 1-10% survival level, followed by single colony regrowth.
Main Results:
- Varying degrees of PDT resistance were successfully induced in the human cell lines.
- The three HT29-derived variants exhibited the most significant resistance.
- Increased survival ratios at the LD90 level ranged from 1.5- to 2.62-fold in the resistant HT29 variants.
Conclusions:
- The study successfully generated PDT-resistant human cancer cell lines, including HT29 variants with notable resistance.
- These cell lines provide a valuable tool for elucidating the complex mechanisms of photodynamic therapy resistance.
- Further research using these models can inform strategies to overcome PDT resistance in clinical settings.
