Ganoderan (GDN) Regulates The Growth, Motility And Apoptosis Of Non-Small Cell Lung Cancer Cells Through ERK Signaling Pathway In Vitro And In Vivo

Background: Lung cancer is the most common malignant tumor worldwide. About 90% of lung cancers are considered non-small cell lung cancer (NSCLC). Ganoderan (GDN) is one of the components of Ganoderma lucidum polysaccharides. Ganoderan A (GDNA), Ganoderan B (GDNB) and Ganoderan C (GDNC) were three polysaccharides isolated from the Ganoderma lucidum fruiting body. Methods: Cell growth was measured by Cell Counting kit-8 and colony formation assay, while cell motility was measured by transwell assay and wound healing assay. Apoptosis was measured by flow cytometry analysis and TUNEL staining, and protein expression was detected by Western blotting and immunohistochemistry. Results: Previous studies have shown that GDNB has the effects of hyperglycemic and kidney protection. However, the role of GDNB in tumors is currently unknown. This study elaborated the role of GDNB in NSCLC and its underlying molecular mechanisms. The results exerted that GDNB inhibited the growth of H510A and A549 cells by suppressing the expression of ki67 and PCNA. Besides, transwell assay and wound healing assay showed that GDNB inhibited invasion and migration of H510A and A549 cells in a concentration-dependent manner. Moreover, Western blotting also showed that GDNB downregulated the levels of N-cadherin, vimentin and Snail in H510A and A549 cells in a dose-dependent manner, while it upregulated the level of E-cadherin. Additionally, GDNB also promoted apoptosis of H510A and A549 cells by regulating the expression of Bcl-2, Bax, cleaved caspase 3 and cleaved PARP. Animal experiments revealed that GDNB inhibited tumor growth and metastasis, and induced apoptosis of tumor cells in vivo. Mechanically, GDNB suppressed the expression of Ras and c-Myc, and decreased the phosphorylation levels of MEK1/2 and ERK1/2. Conclusion: Collectively, all data suggest that GDNB regulates the growth, motility and apoptosis of non-small cell lung cancer cells through ERK signaling pathway in vitro and in vivo.