From the Department of Surgery.
Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa Carver College of Medicine, Iowa City, IA.
Pancreas. 2022 Jul 1;51(6):684-693. doi: 10.1097/MPA.0000000000002086. Epub 2022 Sep 13.
Pharmacological ascorbate (P-AscH - , high-dose, intravenous vitamin C) has shown promise as an adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) treatment. The objective of this study was to determine the effects of P-AscH - when combined with PDAC chemotherapies.
Clonogenic survival, combination indices, and DNA damage were determined in human PDAC cell lines treated with P-AscH - in combination with 5-fluorouracil, paclitaxel, or FOLFIRINOX (combination of leucovorin, 5-fluorouracil, irinotecan, oxaliplatin). Tumor volume changes, overall survival, blood analysis, and plasma ascorbate concentration were determined in vivo in mice treated with P-AscH - with or without FOLFIRINOX.
P-AscH - combined with 5-fluorouracil, paclitaxel, or FOLFIRINOX significantly reduced clonogenic survival in vitro. The DNA damage, measured by γH2AX protein expression, was increased after treatment with P-AscH - , FOLFIRINOX, and their combination. In vivo, tumor growth rate was significantly reduced by P-AscH - , FOLFIRINOX, and their combination. Overall survival was significantly increased by the combination of P-AscH - and FOLFIRINOX. Treatment with P-AscH - increased red blood cell and hemoglobin values but had no effect on white blood cell counts. Plasma ascorbate concentrations were significantly elevated in mice treated with P-AscH - with or without FOLFIRINOX.
The addition of P-AscH - to standard of care chemotherapy has the potential to be an effective adjuvant for PDAC treatment.
药物性抗坏血酸（P-AscH-，大剂量，静脉注射维生素 C）作为胰腺导管腺癌（PDAC）治疗的辅助疗法显示出良好的效果。本研究的目的是确定 P-AscH-与 PDAC 化疗联合使用的效果。
在人 PDAC 细胞系中，用 P-AscH-联合 5-氟尿嘧啶、紫杉醇或 FOLFIRINOX（亚叶酸、5-氟尿嘧啶、伊立替康、奥沙利铂的联合）处理后，测定克隆存活、合并指数和 DNA 损伤。在接受 P-AscH-联合或不联合 FOLFIRINOX 治疗的小鼠体内，测定肿瘤体积变化、总生存期、血液分析和血浆抗坏血酸浓度。
P-AscH-联合 5-氟尿嘧啶、紫杉醇或 FOLFIRINOX 显著降低体外克隆存活。用 P-AscH-、FOLFIRINOX 及其联合处理后，γH2AX 蛋白表达增加，表明 DNA 损伤增加。体内，P-AscH-、FOLFIRINOX 及其联合治疗显著降低肿瘤生长速度。P-AscH-与 FOLFIRINOX 的联合治疗显著延长总生存期。P-AscH-治疗可增加红细胞和血红蛋白值，但对白细胞计数无影响。接受 P-AscH-联合或不联合 FOLFIRINOX 治疗的小鼠血浆抗坏血酸浓度显著升高。
将 P-AscH-添加到标准护理化疗中可能成为 PDAC 治疗的有效辅助手段。
