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KMID : 1001020030010010064
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Journal of Urologic Oncology
2003 Volume.1 No. 1 p.64 ~ p.71
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Expression of BAX in cis-diamminedichloroplatinum (II) Resistant Human Bladder Carcinoma Cell Lines
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Lee Kyung-Chul
Byun Seok-Soo
Yeo Woon-Geol
Paick Jae-Seung
Lee Chong-Wook
Lee Eun-Sik
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Abstract
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Purpose: cis-diamminedichloroplatinum(II)(cisplatin) is well known as the effective anti-chemotherapeutical agent against invasive bladder tumor. However, the response is often limited due to appearance of drug-resistant tumor cells. We established four cisplatin-resistant cell lines sequentially, T24/R0.5, T24/R1, T24/R1.5 and T24/R2, by the stepwise exposure of T24 human bladder cancer cells to increasing concentrations of cisplatin. The purpose of this study is to investigate the expression of Bcl-2 and Bax, apoptotic regulator protein, in cisplatin-resistant human bladder cancer cell lines and their association with development of cisplatin resistance.
Materials and Methods: To compare apoptotic degree between parental and resistant cell lines, flow cytometry and ApopTaq staining were done. The expression of Bcl-2 and Bax protein was demonstrated through Western blotting assay and the relative concentration ratio was calculated using laser densitometry.
Results: The apoptotic population was less in resistance cell lines than parental cell line and no difference was found among resistance cell lines. Expression of Bax significantly decreased in all drug-resistant cells, and the degree of decrease was correlated with cisplatin concentration. Bcl-2 was not detected in all cell lines.
Conclusions: These results suggest that down-regulation of Bax plays an important role in the initial development of cisplatin-resistance in bladder cancer cells. Further studies might be necessary to investigate the interaction of apoptotic regular proteins including p53, Bcl-2 and Bax in apoptotic process.
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KEYWORD
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Bladder cancer, Cisplatin-resistance, Apoptosis, Bcl-2, Bax
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