Abstract
This study was aimed to investigate the anti-tumor, anti-metastasis and immunomodulatory effects of Yifei Tongluo (YFTL), a Chinese herbal formula, in Lewis lung carcinoma mice and to explore the underlying mechanisms. LLC cells were inoculated subcutaneously in C57BL/6 mice to establish the Lewis lung carcinoma model. We observed that YFTL effectively inhibited tumor growth and prolonged the overall survival of tumor-bearing mice. Additionally, YFTL treatment resulted in a significantly decreased number of surface lung metastatic lesions compared with the model control group. Meanwhile, TUNEL staining confirmed that the tumors from YFTL-treated mice exhibited a markedly higher apoptotic index. The results suggest that Akt and mitogen-activated protein kinase (MAPKs) pathways may be involved in YFTL-induced apoptosis. The results show that YFTL also inhibited the vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2, MMP-9, N-cadherin, and Vimentin expression, but increased E-cadherin expression. Mechanistic studies indicated that YFTL could suppress the angiogenesis and the epithelial-mesenchymal transition (EMT) of the tumor through Akt/ERK1/2 and TGFβ1/Smad2 pathways. In addition, YFTL also showed immunomodulatory activities in improving the immunosuppressive state of tumor-bearing mice. Therefore, our findings could support the development of YFTL as a potential antineoplastic agent and a potentially useful anti-metastatic agent for lung carcinoma therapy.
Highlights
Lung cancer is one of the most common causes of cancer death worldwide with high incidence and mortality among all types of cancer
matrix metalloproteinases (MMP)-2 and MMP-9 are highly expressed in malignant tumors, which degrade an array of extracellular matrix (ECM) proteins, and have a profound impact on cancer progression by influencing angiogenesis, invasion, and migration [11].The epithelial-mesenchymal transition (EMT) plays a crucial role in lung cancer metastasis, which causes poor prognosis and drug-resistance [12,13]
The inhibitory effect of Yifei Tongluo (YFTL) was evaluated in Lewis lung carcinoma mice
Summary
Lung cancer is one of the most common causes of cancer death worldwide with high incidence and mortality among all types of cancer. MMP-2 and MMP-9 are highly expressed in malignant tumors, which degrade an array of ECM proteins, and have a profound impact on cancer progression by influencing angiogenesis, invasion, and migration [11].The EMT plays a crucial role in lung cancer metastasis, which causes poor prognosis and drug-resistance [12,13]. Traditional Chinese medicine (TCM) has been applied to treat lung cancer with a large number of advantages, including a wide range of sources, low costs, fewer side effects, and multiple targets over a long history It has advantages in preventing tumor recurrence and metastasis compared with radiotherapy and chemotherapy [15,16,17]. We explored the mechanisms underlying its action against Lewis lung cancer
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