Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China; School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, China.
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China.
J Ethnopharmacol. 2021 Jun 12;273:113965. doi: 10.1016/j.jep.2021.113965. Epub 2021 Feb 25.
Danggui Buxue Decoction (DBD) as a traditional Chinese medicine (TCM) has been widely used to treat blood deficiency. With the immune regulation and hematopoietic effect, DBD improved the quality of life in non-small-cell lung cancer (NSCLC) patients. We previously reported that DBD sensitized the response of NSCLC to Gemcitabine (Gem); however, the synergism and attenuation mechanism on the combination of Gem and DBD has not yet been elucidated.
To investigate the mechanisms of DBD in enhancing the anticancer activity of Gem and alleviating Gem-induced myelosuppression.
A549 nude mice model was established to study the effect on the combination of Gem and DBD. The organ indices, peripheral blood cells and the hematopoiesis-related cytokines were analyzed in Gem-induced myelosuppressive mice. Then we studied the whole process from Gem-induced bone marrow suppression to self-healing, and the mechanism of DBD's attenuation by the experiments of bone marrow nucleated cells (BMNCs).
There were an enhanced anticancer effect and an improvement of hematopoietic function by combining of Gem and DBD in A549 nude mice model. DBD regulated Hu antigen R (HuR), deoxycytidine kinase (dCK) and nuclear factor erythroid 2-related factor (Nrf2), increased the expression of thrombopoietin (TPO) and granulocyte-macrophage colony stimulating factor (GM-CSF). For Gem-induced myelosuppressive mice, DBD improved the number of peripheral blood cells and the levels of hematopoiesis-related cytokines. Moreover, DBD was observed to reduce deoxyribonucleic acid (DNA) content at the G1 phase, promoted BMNCs proliferation and up-regulated cycle-related proteins.
The results indicated that DBD not only improved the sensitivity of Gem but also alleviated Gem-induced myelosuppression. This study may provide a pharmacological basis for the combination of DBD and Gem in clinical application.
当归补血汤（DBD）作为一种中药，已被广泛用于治疗血虚。DBD 具有免疫调节和造血作用，可提高非小细胞肺癌（NSCLC）患者的生活质量。我们之前报道过，DBD 可增强 NSCLC 对吉西他滨（Gem）的反应；然而，Gem 和 DBD 联合的协同作用和衰减机制尚未阐明。
研究 DBD 增强 Gem 抗癌活性和减轻 Gem 诱导的骨髓抑制的作用机制。
建立 A549 裸鼠模型，研究 Gem 和 DBD 联合的作用。分析 Gem 诱导的骨髓抑制小鼠的器官指数、外周血细胞和造血相关细胞因子。然后，我们通过骨髓有核细胞（BMNCs）的实验研究了从 Gem 诱导的骨髓抑制到自我修复的全过程，以及 DBD 衰减的机制。
在 A549 裸鼠模型中，Gem 和 DBD 的联合具有增强的抗癌作用和改善造血功能。DBD 调节 Hu 抗原 R（HuR）、脱氧胞苷激酶（dCK）和核因子红细胞 2 相关因子（Nrf2），增加血小板生成素（TPO）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的表达。对于 Gem 诱导的骨髓抑制小鼠，DBD 可增加外周血细胞数量和造血相关细胞因子水平。此外，DBD 观察到降低 G1 期脱氧核糖核酸（DNA）含量，促进 BMNCs 增殖和上调细胞周期相关蛋白。
结果表明，DBD 不仅提高了 Gem 的敏感性，而且减轻了 Gem 诱导的骨髓抑制。本研究可为 DBD 和 Gem 在临床应用中的联合提供药理学基础。
