Institute of Transfusion Medicine, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, PR China.
Exp Biol Med (Maywood). 2012 Apr;237(4):362-71. doi: 10.1258/ebm.2011.011193. Epub 2012 Apr 4.
Heme oxygenase-1 (HO-1) potently influences tumor growth and metastasis. To date, no study has been performed on HO-1 expression pattern and its clinicopathological significance in human gastric cancer (GC) cases. In this study, the expression of HO-1 in human GC tissues (n = 74) and matched non-tumoral adjacent parenchyma (n = 46) was investigated by immunohistochemistry. The correlation of HO-1 with the clinicopathological characteristics was analyzed. Results showed that HO-1 was expressed in 62 GC tissues from 74 cases (83.8%), which is significantly higher than non-tumoral adjacent parenchyma (20/46, 43.8%, P < 0.05). A high HO-1 expression rate showed a close association with well/moderate histological differentiation and negative lymph node metastasis (P < 0.05). The expression of matrix metallopeptidase 9 (MMP9) and vascular endothelial growth factor A (VEGF-A) as well as chemosensitivity to cisplatin of MKN-45 cell lines with genetically altered HO-1 status were then determined by realtime polymerase chain reaction and 3-(4,5 dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), respectively. Whether the induction or inhibition of HO-1 by cobalt-protoporphyrin-IX (CoPP) or zinc-protoporphyrin-IX (ZnPP) could affect the sensitivity of MKN-45 cells to cisplatin was also studied. Results showed that the expression of MMP9 and VEGF-A were up-regulated in MKN-45 cells overexpressing HO-1, and down-regulated in HO-1 interfered cells. HO-1 overexpression could lead to an increased resistance to cisplatin, whereas down-regulation of HO-1 expression by siRNA or chemical inhibition of HO-1 could lead to increased chemosensitivity to cisplatin in MKN-45 cells. HO-1 may have multiple effects on protection against carcinogenesis and progression in GC.
血红素加氧酶-1（HO-1）强烈影响肿瘤生长和转移。迄今为止，尚无研究探讨 HO-1 在人类胃癌（GC）病例中的表达模式及其临床病理意义。本研究通过免疫组织化学法检测了 74 例 GC 组织（n=74）及其配对的非肿瘤邻近实质（n=46）中 HO-1 的表达情况，并分析了 HO-1 与临床病理特征的相关性。结果显示，74 例 GC 组织中有 62 例（83.8%）表达 HO-1，显著高于非肿瘤邻近实质（20/46，43.8%，P＜0.05）。高 HO-1 表达率与良好/中度组织学分化和阴性淋巴结转移密切相关（P＜0.05）。然后通过实时聚合酶链反应和 3-(4,5 二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）分别测定具有遗传改变 HO-1 状态的 MKN-45 细胞系中基质金属蛋白酶 9（MMP9）和血管内皮生长因子 A（VEGF-A）的表达以及对顺铂的化疗敏感性。还研究了钴原卟啉-IX（CoPP）或锌原卟啉-IX（ZnPP）对 HO-1 的诱导或抑制是否会影响 MKN-45 细胞对顺铂的敏感性。结果显示，HO-1 过表达的 MKN-45 细胞中 MMP9 和 VEGF-A 的表达上调，而 HO-1 干扰细胞中则下调。HO-1 过表达可导致对顺铂的耐药性增加，而 siRNA 下调 HO-1 表达或化学抑制 HO-1 可导致 MKN-45 细胞对顺铂的化疗敏感性增加。HO-1 可能对 GC 中的致癌发生和进展具有多种保护作用。
