背景:光动力疗法(PDT)多年来由于其最小的侵袭性,已被用作有希望的替代癌症治疗。外源性5-氨基乙酰丙酸(ALA)触发原卟啉IX(PpIX)的积累,这发生在癌细胞中。然而,某些类型的癌症在PpIX积累机制中表现出降低的有效性。本研究旨在确定ALA-PDT联合血红素对胃癌TMK-1细胞的影响。
方法:本研究利用TMK-1胃癌细胞系评估PpIX,ROS,和服用ALA后的Fe2+积累,血红素,以及ALA和血红素PDT的组合。我们还评估了与铁稳态相关的mRNA表达和治疗对细胞活力的影响。
结果:ALA和血红素PDT的共同添加持续4小时的处理导致细胞活力显著降低多达18%。虽然ALA-PDT增强了PpIX代谢,血红素的添加通过诱导Fe2积累和影响IRP的mRNA水平来影响活性氧(ROS)的产生和细胞铁稳态,Tfr1,铁蛋白,NFS1和SDHB。
结论:这些研究结果表明,添加ALA和血红素可增强TMK-1细胞的光毒性。ALA和血红素与PDT的组合诱导细胞死亡,细胞毒性特性增加,如PpIX和ROS,随着TMK-1胃癌铁稳态的显著变化。因此,ALA和血红素的组合可能是未来癌症光动力疗法的替代方案之一.
BACKGROUND: Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid (ALA) triggers protoporphyrin IX (PpIX) accumulation, which happens in cancer cells. However, certain types of cancer exhibit reduced effectiveness in the PpIX accumulation mechanism. This study aimed to determine the effect of ALA-PDT combination with
hemin on gastric carcinoma TMK-1 cells.
METHODS: This study utilized TMK-1 gastric cancer cell line to evaluate PpIX, ROS, and Fe2+ accumulation following the administration of ALA,
hemin, and a combination of ALA and
hemin PDT. We also evaluate the mRNA expressions related to iron homeostasis and treatment impacts on cell viability.
RESULTS: The co-addition of ALA and
hemin PDT for 4 h of treatment resulted in a significant decrease in cell viability by up to 18 %. While ALA-PDT enhanced PpIX metabolism, the addition of hemin influenced both the production of reactive oxygen species (ROS) and cellular iron homeostasis by inducing Fe2+ accumulation and affecting mRNA levels of IRP, Tfr1, Ferritin, NFS1, and SDHB.
CONCLUSIONS: These findings suggest that the addition of ALA and hemin enhances phototoxicity in TMK-1 cells. The combination of ALA and hemin with PDT induces cell death, evidenced by increased cytotoxicity properties such as PpIX and ROS, along with significant changes in TMK-1 gastric cancer iron homeostasis. Therefore, the combination of ALA and
hemin could be one of the alternatives in photodynamic therapy for cancer in the future.