药理学抗坏血酸增强胰腺导管腺癌的化疗效果。

Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma.

机构信息

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.

出版信息

Pancreas. 2022 Jul 1;51(6):684-693. doi: 10.1097/MPA.0000000000002086. Epub 2022 Sep 13.

DOI:10.1097/MPA.0000000000002086

PMID:36099493

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9547864/

Abstract

OBJECTIVES

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

The addition of P-AscH - to standard of care chemotherapy has the potential to be an effective adjuvant for PDAC treatment.

摘要

目的

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。

方法

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。

结果

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。