Department of Gastroenterology and Gastrointestinal Oncology, University Medicine Goettingen, 37075 Goettingen, Germany.
Department of Physics and Astronomy, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Cells. 2019 Jun 9;8(6):563. doi: 10.3390/cells8060563.
Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to standard chemo- and radiotherapy. Recently, a new class of non-platinum-based halogenated molecules (called FMD compounds) was discovered that selectively kills cancer cells. Here, we investigate the potential of 1,2-Diamino-4,5-dibromobenzene (2Br-DAB) in combination with standard chemotherapy and radiotherapy in murine and human PDAC. Cell viability and colony formation was performed in human (Panc1, BxPC3, PaTu8988t, MiaPaCa) and three murine (KPC) pancreatic cancer cell lines. In vivo, preclinical experiments were conducted in (KC) and KPC mice using 2Br-DAB (7 mg/kg, i.p.), +/- radiation (10 × 1.8 Gy), gemcitabine (100 mg/kg, i.p.), or a combination. Tumor growth and therapeutic response were assessed by high-resolution ultrasound and immunohistochemistry. 2Br-DAB significantly reduced cell viability in human and murine pancreatic cancer cell lines in a dose-dependent manner. In particular, colony formation in human Panc1 cells was significantly decreased upon 25 µM 2Br-DAB + radiation treatment compared with vehicle control ( = 0.03). In vivo, 2Br-DAB reduced tumor frequency in KC mice. In the KPC model, 2Br-DAB or gemcitabine monotherapy had comparable therapeutic effects. Furthermore, the combination of gemcitabine and 2Br-DAB or 2Br-DAB and 18 Gy irradiation showed additional antineoplastic effects. 2Br-DAB is effective in killing pancreatic cancer cells in vitro. 2Br-DAB was not toxic in vivo, and additional antineoplastic effects were observed in combination with irradiation.
胰腺导管腺癌 (PDAC) 对标准的化疗和放疗具有高度抗性。最近，发现了一类新的非铂类卤代分子（称为 FMD 化合物），它们选择性地杀死癌细胞。在这里，我们研究了 1,2-二氨基-4,5-二溴苯（2Br-DAB）与标准化疗和放疗联合在鼠和人 PDAC 中的潜力。在人（Panc1、BxPC3、PaTu8988t、MiaPaCa）和三种鼠（KPC）胰腺癌细胞系中进行了细胞活力和集落形成实验。在体内，在 KC 和 KPC 小鼠中进行了 2Br-DAB（7 mg/kg，腹腔注射）， +/- 辐射（10×1.8 Gy），吉西他滨（100 mg/kg，腹腔注射）或联合治疗的临床前实验。通过高分辨率超声和免疫组织化学评估肿瘤生长和治疗反应。2Br-DAB 以剂量依赖性方式显著降低人胰腺癌细胞系和鼠胰腺癌细胞系的细胞活力。特别是，与载体对照相比，25 µM 2Br-DAB+辐射处理显著降低了人 Panc1 细胞的集落形成（=0.03）。在体内，2Br-DAB 降低了 KC 小鼠的肿瘤发生率。在 KPC 模型中，2Br-DAB 或吉西他滨单药治疗具有相当的治疗效果。此外，吉西他滨和 2Br-DAB 的联合或 2Br-DAB 和 18 Gy 照射的联合显示出额外的抗肿瘤作用。2Br-DAB 在体外有效杀伤胰腺癌细胞。2Br-DAB 在体内无毒性，与照射联合观察到额外的抗肿瘤作用。
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