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Low-dose photodynamic therapy-induced increase in the metastatic potential of pancreatic tumor cells and its blockade by simvastatin.
Journal of Photochemistry and Photobiology B: Biology ( IF 3.9 ) Pub Date : 2020-05-01 , DOI: 10.1016/j.jphotobiol.2020.111889
Yujie Shen 1 , Mingming Li 1 , Fang Sun 1 , Yi Zhang 1 , Chunying Qu 1 , Min Zhou 1 , Feng Shen 1 , Leiming Xu 1
Affiliation  

Pancreatic tumor are a deadly malignancy with high aggressiveness, and photodynamic therapy (PDT) is a prospective remedy. Nevertheless, the cells in the peripheral tissues of large tumors are often subjected to low-dose illumination and tend to survive after sublethal PDT exposure. Thus, it is of critical importance to determine the metastatic influence of PDT on pancreatic neoplasms. (17R, 18R)-2-(1-Hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt (YLG-1) is a novel chlorine derivative photosensitizer, and we previously demonstrated potent growth inhibition of pancreatic neoplasms by YLG-1-mediated PDT (YLG-1-PDT). In this study, we assessed the metastatic effect of low-dose PDT with YLG-1 on pancreatic tumors and its combination with simvastatin. We found that sublethal YLG-1-PDT promoted MMP-2/9 expression in residual pancreatic tumor cells as well as tumor cell motility/invasion and liver metastasis. Since simvastatin was reported to improve the survival of patients with pancreatic tumors at an early stage and suppress the metastasis of most cancers, we utilized it during YLG-1-PDT and discovered alleviated migration/invasion, metastasis and MMP-2/9 expression. Collectively, our study results raise the concern that PDT could also be a Janus-like treatment owing to its prometastatic potential provoked by a low dosage. Concomitant use of simvastatin during PDT might be an effective method to attenuate such adverse reactions.

中文翻译:

小剂量光动力疗法诱导的胰腺肿瘤细胞转移潜力的增加及其辛伐他汀的阻滞作用。

胰腺肿瘤是致命的恶性肿瘤,具有很高的侵袭性,而光动力疗法(PDT)是一种前瞻性治疗方法。然而,大肿瘤周围组织中的细胞经常受到低剂量照射,并倾向于在亚致死性PDT暴露后存活。因此,确定PDT对胰腺肿瘤的转移影响至关重要。(17R,18R)-2-(1-己氧基乙基)-2-二乙烯基氯E6三钠盐(YLG-1)是一种新型的氯衍生物光敏剂,我们先前证明了YLG-1介导的PDT对胰腺肿瘤的有效生长抑制作用(YLG-1-PDT)。在这项研究中,我们评估了低剂量PDT与YLG-1对胰腺肿瘤及其与辛伐他汀联合治疗的转移作用。我们发现亚致死性YLG-1-PDT促进了残留胰腺肿瘤细胞中MMP-2 / 9的表达以及肿瘤细胞的运动/侵袭和肝转移。由于据报道辛伐他汀可以改善胰腺癌患者的早期生存率并抑制大多数癌症的转移,因此我们在YLG-1-PDT期间使用了辛伐他汀,发现其迁移/侵袭,转移和MMP-2 / 9表达均得到缓解。总的来说,我们的研究结果引起了人们的关注,因为低剂量的PDT具有潜在的转移潜力,因此它也可能是Janus样的治疗方法。PDT期间同时使用辛伐他汀可能是减轻此类不良反应的有效方法。由于据报道辛伐他汀可改善胰腺癌患者的早期生存率并抑制大多数癌症的转移,因此我们在YLG-1-PDT期间使用了辛伐他汀,发现其迁移/侵袭,转移和MMP-2 / 9表达均得到缓解。总的来说,我们的研究结果引起了人们的关注,因为低剂量的PDT具有潜在的转移潜力,因此它也可能是Janus样的治疗方法。PDT期间同时使用辛伐他汀可能是减轻此类不良反应的有效方法。由于据报道辛伐他汀可改善胰腺癌患者的早期生存率并抑制大多数癌症的转移,因此我们在YLG-1-PDT期间使用了辛伐他汀,发现其迁移/侵袭,转移和MMP-2 / 9表达均得到缓解。总的来说,我们的研究结果引起了人们的关注,因为低剂量的PDT具有潜在的转移潜力,因此它也可能是Janus样的治疗方法。PDT期间同时使用辛伐他汀可能是减轻此类不良反应的有效方法。
更新日期:2020-05-01
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