The TCM Prescription Yi-Fei-Jie-Du-Tang Inhibit Invasive Migration and EMT of Lung Cancer Cells by Activating Autophagy.

Shanshan Wang,Xiaojun Dai,Qingyin Wang,Zaichuan Wang,Yinqiu Wu,Chao Qian,Yongjian Wu,Chao Hou,Xiaochun Zhang,Meng-Shih Weng

doi:10.1155/2022/9160616

Abstract

Yi-Fei-Jie-Du-Tang (YFJDT) is a traditional Chinese medicine formulation. Our previous studies have demonstrated that YFJDT can be used to treat non-small-cell lung cancer (NSCLC), but its protective effect against NSCLC and its mechanisms remain unclear. In the present study, we evaluated the protective effects and potential mechanisms of YFJDT on a tumor-bearing mouse lung cancer model and A549 cell model. Tumor-bearing mice and A549 cells were treated with YFJDT, tumors were measured during the experiment, and tumor tissues and cell supernatants were collected at the end of the experiment to assess the levels of autophagy and epithelial-mesenchymal transition (EMT)-related proteins. The results showed that YFJDT treatment reduced tumor volume and mass, increased the expression of the autophagy marker LC3, and inhibited EMT-related proteins compared with the model group. Cell survival was reduced in the YFJDT-treated groups compared with the model group, and YFJDT also reduced the migration and invasion ability of A549 cells in a dose-dependent manner. Western blotting detected that YFJDT also upregulated FAT4 in the tumor tissue and A549 cells and downregulated the expression of vimentin. Meanwhile, apoptosis in both tissues and cells was greatly increased with treatment of YFJDT. We further interfered with FAT4 expression in cells and found that the inhibitory effect of YFJDT on EMT was reversed, indicating that YFJDT affects EMT by regulating FAT4 expression. Taken together, results of this study suggested that the inhibitory effect of YFJDT on EMT in lung cancer tumors is through upregulating FAT4, promoting autophagy, and thus inhibiting EMT in cancer cells.

Highlights

Lung cancer is currently one of the major malignancies threatening human health, with the highest incidence and mortality rate [1]
Recent research studies have shown that autophagy affects the invasion and metastasis of tumor cells by regulating Epithelial-mesenchymal transition (EMT) [6, 7]. us, modulation of autophagy to inhibit the development of tumor has become a new direction in tumor therapy
Cell proliferation was assayed at different times, and it was found that the cell proliferation capacity of the administered group decreased significantly with time compared to the model group in a dose-dependent manner (p < 0.05, Figure 4(a)). e efficacy of YFJDT was further validated when we examined the invasive and migratory capacity of YFJDT-treated A549 cells using the transwell assay and cell scratch assay. e transwell migration assay data showed that YFJDT significantly inhibited cell invasion of A549 cells and that higher concentrations of YFJDT-containing serum had a better inhibitory effect than lower concentrations (p < 0.05, Figure 4(b))

Summary

Introduction

Lung cancer is currently one of the major malignancies threatening human health, with the highest incidence and mortality rate [1]. Non-small-cell lung cancer (NSCLC) is the most predominant type of lung cancer, and metastasis is its malignant feature and an important factor affecting patient survival and prognosis [2, 3]. How to suppress metastasis is a key breakthrough tool that promote the prognosis of lung cancer patients. Epithelial-mesenchymal transition (EMT) is involved in the invasion and metastasis of lung cancer and plays an important role in them [4, 5]. Recent research studies have shown that autophagy affects the invasion and metastasis of tumor cells by regulating EMT [6, 7]. (Beishashen), Ophiopogon japonicus (L.f.) Ker-Gawl (Maidong), Pseudostellaria heterophylla (Miq.) Pax ex Pax et Hoffm. Liang. (Shancigu), Sarcandra glabra ( unb.) Nakai. (Zhongjiefeng), Ranunculus ternatus unb. (Maozhuacao), Baijiangcan, Oldenlandia diffusa

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