1. Danggui Buxue Decoction enhances the anticancer activity of gemcitabine and alleviates gemcitabine-induced myelosuppression.
- Author
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Liu, Yan, Chang, Ming, Hu, Zhaoliang, Xu, Xin, Wu, Wei, Ning, Manru, Hang, Taijun, and Song, Min
- Subjects
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LUNG cancer , *CYTOKINES , *MEDICINAL plants , *ANIMAL experimentation , *IMMUNOSUPPRESSION , *ANTINEOPLASTIC agents , *ANTIMETABOLITES , *PLANT extracts , *CHINESE medicine , *MICE , *PHARMACODYNAMICS - Abstract
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. [Display omitted] • The combination of Gem and DBD has enhanced anticancer effect and improved the hematopoietic function. • Danggui Buxue Decoction improved the sensitivity of gemcitabine through regulating the expressions of Hu antigen R (HuR), deoxycytidine kinase (dCK), nuclear factor erythroid 2-related factor (Nrf2). • For the first time, we studied the whole process from gemcitabine-induced bone marrow suppression to self-healing, and the mechanism of Danggui Buxue Decoction's attenuation. • Danggui Buxue Decoction alleviated gemcitabine-induced myelosuppression via promoting cell cycle transformation and regulating cycle-related proteins in bone marrow nucleated cells. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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