Ito Hiromu, Matsui Hirofumi
University of Tsukuba, Faculty of Medicine, Tsukuba, Japan.
University of Tsukuba, Faculty of Medicine, Tsukuba, Japan; Kyoto Prefectural University of Medicine, Kyoto, Japan.
Laser Ther. 2016 Oct 1;25(3):193-199. doi: 10.5978/islsm.16-OR-15.
Worldwide, the number of cancer cases is increasing. Typically, they are treated by either surgery or chemotherapy. However, these treatments may be undesirable in elderly patients or those who are under medication with antiplatelet drugs. Photodynamic therapy (PDT) represents a potentially attractive treatment option for these types of patients, since it does not involve surgery and has considerably reduced side effects compared to chemotherapy. Porphyrin, one of the most commonly used photosensitizers, has the convenient property of cancer-specific accumulation and therefore, is commonly used in PDT. However, the mechanism by which this cancer-specific accumulation occurs remains unclear. We previously reported that a heme-transport protein, HCP1, was capable of transporting porphyrin compounds. HCP1 expression is associated with increased hypoxia, although the detailed mechanism by which this regulation occurs is also unknown. Here, we review available data on the mechanism of regulation of HCP1 expression through mitochondrial reactive oxygen species (mitROS). Specifically, cancer cells show increased expression of HCP1 compared to normal cells and this over-expression is reduced in cancer cells over-expressing the mitROS scavenging enzyme manganese superoxide dismutase (MnSOD). Thus we conclude that mitROS is involved in regulating HCP1 expression.
在全球范围内,癌症病例的数量正在增加。通常,这些病例通过手术或化疗进行治疗。然而,对于老年患者或正在服用抗血小板药物的患者而言,这些治疗方法可能并不适宜。光动力疗法(PDT)对于这类患者来说是一种潜在的有吸引力的治疗选择,因为它不涉及手术,并且与化疗相比副作用大幅减少。卟啉是最常用的光敏剂之一,具有在癌症中特异性积累的便利特性,因此常用于光动力疗法。然而,这种癌症特异性积累发生的机制仍不清楚。我们之前报道过,一种血红素转运蛋白HCP1能够转运卟啉化合物。HCP1的表达与缺氧增加有关,尽管这种调节发生的详细机制也尚不清楚。在此,我们综述了关于通过线粒体活性氧(mitROS)调节HCP1表达机制的现有数据。具体而言,与正常细胞相比,癌细胞中HCP1的表达增加,而在过表达mitROS清除酶锰超氧化物歧化酶(MnSOD)的癌细胞中,这种过表达会降低。因此我们得出结论,mitROS参与调节HCP1的表达。