Miyake H, Hara I, Gohji K, Yoshimura K, Arakawa S, Kamidono S
Department of Urology, Kobe University School of Medicine, Japan.
Cancer Lett. 1998 Jan 30;123(2):121-6. doi: 10.1016/s0304-3835(97)00365-0.
To clarify the role of basic fibroblast growth factor (FGF-2) in the drug resistance of bladder cancer, we transfected the FGF-2 gene into HT1376, an FGF-2 negative human bladder cancer cell line. The FGF-2-transfected cell lines exhibited three- to four-fold higher resistant potential to cisplatin than the vector-only transfected control cell lines in vitro. When cisplatin was injected intraperitoneally after s.c. implantation of HT1376 sublines into nude mice, FGF-2 transfectants formed tumors about twice as large as did controls. In contrast, there was no significant difference in either cell proliferation in vitro or tumor growth in vivo among these cell lines without cisplatin treatment. Furthermore, DNA degradation following cisplatin treatment was markedly suppressed in FGF-2 transfectants compared to control cells. These results suggest that the expression of the FGF-2 gene plays an important role in the acquisition of the cisplatin-resistant phenotype of bladder cancer, probably through the protection against cisplatin-induced apoptosis.
为阐明碱性成纤维细胞生长因子(FGF - 2)在膀胱癌耐药性中的作用,我们将FGF - 2基因转染至HT1376,一种FGF - 2阴性的人膀胱癌细胞系。在体外,转染FGF - 2的细胞系对顺铂的耐药潜力比仅转染载体的对照细胞系高3至4倍。当将HT1376亚系皮下植入裸鼠后腹腔注射顺铂时,FGF - 2转染细胞形成的肿瘤大小约为对照细胞的两倍。相比之下,在没有顺铂处理的情况下,这些细胞系在体外的细胞增殖或体内的肿瘤生长方面均无显著差异。此外,与对照细胞相比,FGF - 2转染细胞中顺铂处理后的DNA降解明显受到抑制。这些结果表明,FGF - 2基因的表达在膀胱癌顺铂耐药表型的获得中起重要作用,可能是通过保护细胞免受顺铂诱导的凋亡。