顺铂耐药膀胱癌细胞系中p73诱导作用的丧失。

Loss of p73 induction in a cisplatin-resistant bladder cancer cell line.

作者信息

Ono Y, Nonomura N, Harada Y, Fukui T, Tokizane T, Sato E, Nakayama M, Nishimura K, Takahara S, Okuyama A

机构信息

Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Mol Urol. 2001 Spring;5(1):25-30. doi: 10.1089/109153601750124267.

DOI:10.1089/109153601750124267

PMID:11689148

Abstract

BACKGROUND

Cisplatin (CDDP) plays an important role in the treatment of transitional-cell carcinoma (TCC), but resistance develops. The mechanism is not entirely understood.

METHODS

To assess acquired resistance to CDDP, we established a CDDP-resistant subclone, CL8-2, of T24, which is a bladder cancer cell line. We examined the changes in the various pathways leading to apoptosis in the parent line and CL8-2.

RESULTS

The drug caused apoptosis of T24 cells but not CL8-2 cells. The CL8-2 cells were 6.4 times more resistant to CDDP than was T24. In both cell lines, the mismatch repair genes hMLH-1 and hMSH-2 were expressed at high levels. The p53 protein was not detected in either cell line but p73 protein was induced by CDDP treatment in T24 cells, which was followed by activation of caspases 3, 8, and 9. This phenomenon was not observed in CL8-2 cells.

CONCLUSION

These results suggest that loss of p73 induction may lead to CDDP resistance of TCC.

摘要

背景

顺铂（CDDP）在移行细胞癌（TCC）治疗中发挥重要作用，但会产生耐药性。其机制尚未完全明确。

方法

为评估对CDDP的获得性耐药，我们建立了T24（一种膀胱癌细胞系）的CDDP耐药亚克隆CL8 - 2。我们检测了亲代细胞系和CL8 - 2中导致细胞凋亡的各种途径的变化。

结果

该药物可诱导T24细胞凋亡，但对CL8 - 2细胞无效。CL8 - 2细胞对CDDP的耐药性是T24细胞的6.4倍。在两种细胞系中，错配修复基因hMLH - 1和hMSH - 2均高表达。两种细胞系中均未检测到p53蛋白，但CDDP处理可诱导T24细胞中p73蛋白表达，随后激活半胱天冬酶3、8和9。CL8 - 2细胞中未观察到此现象。