Synchrotron SOLEIL, L'Orme des Merisiers, 91192 GIF SUR YVETTE, France.
J Photochem Photobiol B. 2010 May 3;99(2):100-4. doi: 10.1016/j.jphotobiol.2010.03.001. Epub 2010 Mar 6.
Photodynamic therapy combines a photosensitizer, localised preferentially in malignant cells with light activation. Hypocrellin A (HA), a lipid-soluble peryloquinone, is considered as a high potential photosensitizer. We report dose and light irradiation effects of HA on HeLa, Calu and K562 cell lines, the latter including a subclone resistant to Imatinib mesylate (IM, Gleevec). All cell lines and subclones tested are sensitive to HA PDT. In the epithelial tumour cell lines, we observe a significant photosensitizing effect in the presence of HA. In the leukemic K562 cells, HA exposure led to an inhibitory effect, which was not seen in the K562 cells resistant to Imatinib mesylate. However, experiments using IM and HA led to a reversal of IM-resistant phenotype in this cell line, with evidence of a major sensitizing effect of photodynamic therapy. Overall our results suggest a phototoxicity of HA in epithelial cell lines and demonstrate for the first time, a synergy between IM and photodynamic therapy to circumvent IM-resistance.
光动力疗法将一种光敏剂与光激活相结合，该光敏剂优先定位于恶性细胞中。竹红菌素 A（HA）是一种脂溶性过氧萘醌，被认为是一种有潜力的光敏剂。我们报告了 HA 对 HeLa、Calu 和 K562 细胞系的剂量和光辐照效应，后者包括对甲磺酸伊马替尼（IM，格列卫）耐药的亚克隆。所有测试的细胞系和亚克隆对 HA PDT 均敏感。在上皮肿瘤细胞系中，我们观察到在 HA 存在下存在明显的光致敏作用。在白血病 K562 细胞中，HA 暴露导致抑制作用，而在对甲磺酸伊马替尼耐药的 K562 细胞中则没有观察到。然而，使用 IM 和 HA 的实验导致该细胞系中 IM 耐药表型的逆转，证明光动力疗法具有主要的增敏作用。总体而言，我们的结果表明 HA 在上皮细胞系中具有光毒性，并首次证明了 IM 和光动力疗法之间的协同作用，以规避 IM 耐药性。
