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Study on the Increased Susceptibility to Cisplatin

Cordycepin에 대해 유도되는 cisplatin 감수성 증가에 대한 연구,

마티 하마디 (Madhi, Hamadi, 경상대학교 대학원)

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In this study, I investigate the cordycepin-mediated sensitization to cisplatin using cisplatin-resistant human bladder cancer cell line, T24R2. Cordycepin is a derivative of nucleoside adenosine which was initially extracted from fungi of genus Cordyceps. Whereas only cisplatin 2 µg/ml treatment d...
In this study, I investigate the cordycepin-mediated sensitization to cisplatin using cisplatin-resistant human bladder cancer cell line, T24R2. Cordycepin is a derivative of nucleoside adenosine which was initially extracted from fungi of genus Cordyceps. Whereas only cisplatin 2 µg/ml treatment did not induce apoptosis in T24R2, cordycepin co-treatment with cisplatin significantly increased apoptosis in T24R2. Cordycepin helped loss of mitochondrial stability resulted in caspase-dependent apoptosis induced by cisplatin treatment. Cordycepin broke the balance of pro- and anti-apoptotic proteins in T24R2 treated with cisplatin: decrease of antiapoptotic proteins, Bcl-2, Bcl-xL, and Mcl-1, and an increase of pro-apoptotic proteins, Bak and Bax. The resistance to cisplatin of T24R2 was associated with MDR1 which pumps out drugs from the intracellular compartment to the extracellular environment. Cordycepin negatively regulated MDR1 expression at transcriptional level and knockdown of MDR1 expression sensitized T24R2 to cisplatin. Therefore, we suggest that cordycepin sensitizes T24R2 to cisplatin through downregulation of MDR1 expression.
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Introduction 1
Materials and Methods 6
Cell lines and cultures 6
...
Introduction 1
Materials and Methods 6
Cell lines and cultures 6
Antibodies and reagents 6
MTT assay 7
PI staining 7
RNA isolation and semi-quantitative RT-PCR analysis 8
Immunoblotting analysis 8
Confocal microscopy 9
TUNEL assay 9
Rhodamine123 uptake/retention assay 10
Construction of luciferase reporter plasmid and dual luciferase assay 10
Statistical analysis 11
Results 12
1. Cordycepin combined to cisplatin induced cell death in T24R2 cells 12
2. Cordycepin combined to cisplatin induced apoptosis in T24R2 cells 16
3. Cordycepin combined to cisplatin induced apoptosis in T24R2 cells through the mitochondrial pathway 19
4. Cordycepin induced apoptosis in T24R2 cells by down-regulating MDR1 expression 25
5. Cordycepin sensitized T24R2 cells to cisplatin by inhibiting the activity of MDR1 promoter 31
Discussion 35
References 40