印度靛绿和化疗联合光动力疗法在肝细胞癌细胞系和小鼠模型中的协同增效作用。
Synergistic effects of concurrent photodynamic therapy with indocyanine green and chemotherapy in hepatocellular carcinoma cell lines and mouse models.
发表日期:2023 Feb
作者:
Jae Sun Park, Sohyun Park, Sang-Jae Park, Seok-Ki Kim
来源:
J Photoch Photobio B
摘要:
光动力疗法(PDT)采用靛青绿(ICG)808纳米激光照射已显示对肝细胞瘤(HCC)同种异移植模型有杀肿瘤效果。最近,PDT与同时化疗的结合也显示出协同效应,对癌症的治疗有更好的疗效。在本研究中,我们采用了ICG联合化疗药物PDoX模型中体内外。我们用索拉非尼或多柔比星增加索拉非尼或多柔比星浓度,增加808纳米光的总能量,独立地在Huh-7和Hep3b细胞系中进行了PDT和化疗。随后,我们将这两种治疗方法结合在一起,以确认对细胞存活率的影响。组合指数(CI)在体外评估,然后在HCC PDoX小鼠模型中进行808纳米激光照射,并用多柔比星进行化疗治疗,共持续12天。随着索拉非尼或多柔比星的浓度增加和808纳米光总能量的增加,Huh-7和Hep3B细胞系的存活率迅速降低。与单独进行PDT或化疗相比,联合PDT和化疗的Huh-7和Hep3b细胞系的存活率更低。组合指数在索拉非尼或多柔比星处理的Huh-7和Hep3b细胞系中<1。在HCC PDoX小鼠模型中,与单一化疗或PDT和对照组相比,肿瘤大小明显减小,完全缓解。PDT与同时化疗在HCC细胞系和PDoX模型中的协同作用得到了证实,未出现明显的不良反应。PDT与同时化疗可在进一步的临床前研究中应用。版权所有©2022 Elsevier B.V.。保留所有权利。
Photodynamic therapy (PDT) using an 808 nm laser irradiation with indocyanine green (ICG) has shown tumoricidal effects in a hepatocellular (HCC) orthotopic xenograft model. Recently, combining PDT with concurrent chemotherapy has shown synergistic outcomes and a better therapeutic effect for cancer treatment. In the present study, we utilized a combination of chemotherapy drugs and PDT using ICG in vitro and in vivo in a patient-derived orthotopic xenograft (PDoX) model.We independently performed PDT and chemotherapy with sorafenib or doxorubicin in the Huh-7 and Hep3b cell lines by increasing the sorafenib or doxorubicin concentration and increasing the total energy of 808 nm light. Subsequently, we combined the two treatments to confirm the effects on cell viability. The combination index (CI) was evaluated in vitro, and thereafter, in the HCC PDoX mouse model, 808 nm laser irradiation with intravenously injected ICG and chemotherapy using doxorubicin were performed for twelve days.The viability of the Huh-7 and Hep3B cell lines decreased rapidly as the concentration of sorafenib or doxorubicin increased and as the total energy of 808 nm light increased. The cell viability of the Huh-7 and Hep3b cell lines with combined PDT and chemotherapy was less than that with PDT or chemotherapy alone. The CI was <1 in the sorafenib- or doxorubicin-treated Huh-7 and Hep3b cell lines. In the HCC PDoX mouse model, tumor size was markedly decreased, and complete remission achieved compared to that of the single chemotherapy or PDT and control groups.The synergistic effect of concurrent PDT and chemotherapy in the HCC cell line and PDoX model was confirmed with no definite adverse effect. Concurrent PDT and chemotherapy could be applied in further preclinical studies.Copyright © 2022 Elsevier B.V. All rights reserved.