Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI.
Department of Pathology, Wayne State University School of Medicine, Detroit, MI.
Photochem Photobiol. 2021 Jul;97(4):837-840. doi: 10.1111/php.13397. Epub 2021 Feb 24.
A concurrent human papilloma virus (HPV) infection potentiates the efficacy of ionizing radiation for treatment of head and neck cancer by promoting apoptosis. Studies in cell culture indicated an opposite effect for photodynamic therapy (PDT) when this leads to mitochondrial and ER photodamage. The explanation for this difference in PDT efficacy remains to be established. While apoptosis was impaired in HPV(-) cells, such cells can be killed via photodamage directed at the ER: this leads to a nonapoptotic death pathway termed paraptosis. No differences in photosensitizer uptake or reactive oxygen species (ROS) production were observed in HPV(+) vs. HPV(-) tumors. We now provide evidence that death pathways initiated by ER/mitochondrial photodamage leading to either paraptosis or apoptosis are impaired in an HPV(+) head and neck cell line. These results illustrate the complex determinants of PDT efficacy, a topic that has yet to be fully explored.
同时感染人乳头瘤病毒（HPV）可通过促进细胞凋亡来提高头颈癌放射治疗的效果。细胞培养研究表明，光动力疗法（PDT）导致线粒体和内质网光损伤时会产生相反的效果。这种 PDT 疗效差异的解释尚待确定。虽然 HPV（-）细胞中的细胞凋亡受到抑制，但可以通过针对内质网的光损伤杀死这些细胞：这会导致一种非凋亡死亡途径，称为 Paraptosis。在 HPV（+）与 HPV（-）肿瘤中，并未观察到光敏剂摄取或活性氧（ROS）产生的差异。我们现在提供的证据表明，导致 Paraptosis 或细胞凋亡的内质网/线粒体光损伤引发的死亡途径在 HPV（+）头颈癌细胞系中受到损害。这些结果说明了 PDT 疗效的复杂决定因素，这一主题尚未得到充分探讨。
