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Published on: March 18, 2014
Photodynamic effect in medulloblastoma: downregulation of matrix metalloproteinases and human telomerase reverse
Ellie Shihng Meir Chu1, Thomas Kwok Shing Wong, Christine Miu Ngan Yow
1Medical Laboratory Science, Department of Health Technology & Informatics, The Hong Kong Polytechnic University, HKSAR.
Abstract:
Tumor invasion and immortality are the most unfavorable drawbacks after cancer treatment. In this study, we focus on determining the photodynamic modulation of the proteolytic enzymes, matrix metalloproteinases (MMP); and a core catalytic subunit of telomerase, the human telomerase reverse transcriptase (hTERT) in medulloblastoma (MED) cell line (TE-671). Hexvix (ALA-H) mediated photodynamic therapy (PDT) demonstrated greater efficacy than 5-aminolevulinic acid (5-ALA) in terms of drug uptake and anti-proliferative effect. Both MMP-2 and hTERT expression are down-regulated quantitatively using ELISA and reverse-transcriptase-PCR (RT-PCR) respectively at post-treatment for this cell line. The MMP-9 expression remains unchanged after treatment. Further, there is a statistically significant inhibition of cell migration at 24 h post-ALA-H-PDT at LD(50) (0.01 mM, 2 J cm(-2); p < 0.001) in MED TE-671 cells. Evidently, MMP-2 and hTERT mRNA expressions can be the targets for the photodynamic intervention on tumor cell migration and immortality. Hence, PDT may be an alternate cancer regime for medulloblastoma.
Insights
Photodynamic therapy using Hexvix (ALA-H) effectively reduced tumor cell invasion and immortality by down-regulating matrix metalloproteinase-2 (MMP-2) and human telomerase reverse transcriptase (hTERT) in medulloblastoma cells.
Area of Science:
- Oncology
- Biochemistry
- Photodynamic Therapy
Background:
- Tumor invasion and immortality pose significant challenges in cancer treatment.
- Matrix metalloproteinases (MMP) and human telomerase reverse transcriptase (hTERT) are key factors in tumor progression.
Purpose of the Study:
- To investigate the photodynamic modulation of MMP and hTERT in medulloblastoma (MED) cells.
- To compare the efficacy of Hexvix (ALA-H) mediated photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA).
Main Methods:
- Utilized medulloblastoma cell line (TE-671).
- Administered Hexvix (ALA-H) mediated photodynamic therapy (PDT).
- Quantified MMP-2 and hTERT expression using ELISA and RT-PCR; assessed cell migration inhibition.
Main Results:
- Hexvix (ALA-H) PDT showed superior drug uptake and anti-proliferative effects compared to 5-ALA.
- MMP-2 and hTERT expressions were significantly down-regulated post-treatment.
- MMP-9 expression remained unchanged.
- Cell migration was significantly inhibited at 24 h post-ALA-H-PDT.
Conclusions:
- MMP-2 and hTERT mRNA expressions are potential targets for photodynamic intervention against tumor cell migration and immortality.
- PDT may serve as an alternative therapeutic strategy for medulloblastoma.
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