Abstract
This study aimed to investigate whether the anti-tumor effect of gemcitabine (GEM) in non-small-cell lung cancer (NSCLC) treatment was affected by Danggui Buxue decoction (DBD), and explore the potential mechanisms. The combined use of GEM and DBD showed an enhanced tumor growth inhibition effect in a murine Lewis lung carcinoma (LLC) model. LC-MS/MS results showed that the pharmacokinetic behaviors of a GEM active metabolite, gemcitabine triphosphate (dFdCTP), were found to be altered remarkably in the peripheral blood mononuclear cells (PBMC) of DBD co-administration rats. In addition, after co-administration of DBD with GEM, Western Blot and qPCR results confirmed that the expression of deoxycytidine kinase (dCK) in tumor tissues of LLC-bearing mice were markedly increased. DBD co-administration also reversed the upregulation of P-glycoprotein (P-gp) in tumor tissues induced by GEM. Moreover, DBD could notably up-regulate the IL-12p70 and GM-CSF expression in mice serum, suggesting potential immunomodulatory activities in tumor-bearing mice. Meanwhile, DBD inhibited the P-gp efflux activity in A549 cells. Therefore, the regulation of dCK and P-gp played important roles in the alternation of GEM pharmacokinetics and the enhancement of the anti-tumor effect of GEM. DBD being a potential dCK promoter could work as an adjuvant agent to boost the anticancer effect of GEM.
Highlights
Lung cancer is the leading cause of cancer death all over the world
By utilizing a Lewis lung carcinoma (LLC) murine model, we evaluated the anti-tumor effect of GEM altered by a combination administration of Danggui Buxue decoction (DBD) and determined the mRNA and protein expression level of deoxycytidine kinase (dCK) and P-gp in tumor tissue of LLC model mice
To evaluate whether the tumor growth inhibition effects of GEM were enhanced by co-administration of DBD, an LLC mouse model was established by subcutaneous injection of LLC cells into the right flank of each C57BL/6 mouse
Summary
Lung cancer is the leading cause of cancer death all over the world. There were an estimated2,093,876 new cases and 1,761,007 deaths all over the world in 2018 [1]. Lung cancer is the leading cause of cancer death all over the world. 2,093,876 new cases and 1,761,007 deaths all over the world in 2018 [1]. Non-small-cell lung cancer (NSCLC), which has a more variable behavior, accounts for about 85% of lung cancers. 18% of the patients suffering from lung cancer are expected to live five years after diagnosis [2]. Chemotherapy is currently the most effective remedy for NSCLC. Despite the improved outcomes for NSCLC patients by various chemotherapeutic drugs, the growing drug resistance and severe side effects have been a major reason for the failure of chemotherapy [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
