Molecular Mechanisms Underlying the Inhibitory Effects ofQingzaojiufei Decoction on Tumor Growth in Lewis Lung Carcinoma

摘要

>Objective: Qingzaojiufei decoction (QD) is an empirical herbal formula from traditional Chinese medicine that is used for the treatment of lung-related diseases. However, the effect of QD on the growth of lung tumor cells has not been investigated. The aim of this study was to examine the antitumor activity of QD in Lewis lung carcinomas (LLC) in vivo and in vitro, and to elucidate the underlying mechanisms. >Methods: The LLC cells were used to assess the antitumor activity of QD by Cell Counting Kit-8 assay in vitro. In vivo, mice were randomly assigned to 5 groups (n = 10/group): the model control (MC) group was intragastrically administered physiological saline (0.9% NaCl) twice daily from day 2 after tumor implantation for 2 weeks. The QD groups were intragastrically administered QD twice daily from 2 weeks before to 2 weeks after tumor implantation for 4 weeks. The mRNA levels were detected by quantitative polymerase chain reaction, the proteins expression was determined by immunohistochemistry or western blotting. >Results: Compared with the model group, QD showed inhibition of proliferation of LLC cells and reductions in tumor weight and proliferating cell nuclear antigen protein expression. Furthermore, QD up-regulated p53 mRNA expression, and downregulatedc-myc and Bcl-2 mRNA expression, while MMP-9, VEGF, and VEGFR protein expressionwas suppressed. Phosphorylated ERK1/2 levels were also reduced by QD in adose-dependent manner. >Conclusion: Our findings suggest that QDinhibited lung tumor growth and proliferation, by activation of tumor suppressorgenes, inactivation of oncogenes, suppressing the potential for invasion andmetastasis, and attenuating angiogenesis. The ERK/VEGF/MMPs signaling pathwaysmay play an important role in QD-induced inhibition of malignant tumor cellproliferation.