Department of Urology, Nara Medical University, Nara, 634-8522, Japan.
Anticancer Res. 2010 Jun;30(6):2145-52.
Elevated heme oxygenase-1 (HO-1) is associated with resistance to chemo- and radiotherapy through anti-apoptotic function. The present study evaluated whether the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP), enhances the cytotoxic effect of gemcitabine in urothelial carcinoma (UC).
The in vitro cytotoxic effect of combination treatment of gemcitabine and ZnPP on UC cells was examined. The in vivo growth inhibitory effects of intraperitoneal administration of gemcitabine and/or ZnPP on mouse subcutaneous tumours were examined. The apoptotic changes were analysed with the detection of DNA fragmentation and cleaved caspase-3.
HO-1 was up-regulated by both gemcitabine and irradiation treatment in vitro. ZnPP sensitised the UC cells to both therapies. Enhanced apoptosis was induced by the ZnPP combined with gemicitabine. ZnPP enhanced the antitumour effect of gemcitabine in vivo along with decreased numbers of proliferating cells and increased numbers of apoptotic cells.
These findings suggest that ZnPP combined with gemcitabine or irradiation therapy may be an effective therapeutic modality for UC patients.
血红素加氧酶-1（HO-1）水平升高通过抗细胞凋亡功能与化疗和放疗抵抗相关。本研究评估了 HO-1 抑制剂锌原卟啉 IX（ZnPP）是否增强了对膀胱癌（UC）的吉西他滨的细胞毒性作用。
检测吉西他滨与 ZnPP 联合治疗对 UC 细胞的体外细胞毒性作用。检测腹腔内给予吉西他滨和/或 ZnPP 对小鼠皮下肿瘤生长的体内抑制作用。通过检测 DNA 片段化和裂解的 caspase-3 分析凋亡变化。
HO-1 可被吉西他滨和体外辐照处理上调。ZnPP 增敏 UC 细胞对这两种治疗方法的敏感性。ZnPP 联合吉西他滨诱导增强的细胞凋亡。ZnPP 增强了吉西他滨在体内的抗肿瘤作用，同时减少了增殖细胞的数量，增加了凋亡细胞的数量。
这些发现表明，ZnPP 联合吉西他滨或放疗可能是 UC 患者的一种有效治疗方式。
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