Bufalin inhibits gefitinib resistant NCI-H460 human lung cancer cell migration and invasion in vitro.
BACKGROUND
Bufalin, a component of Chan Su (frog), has been shown to have biological activities including anti-tumor effects. Gefitinib has been used as an anti-cancer drug in lung cancer patients; however, some patients eventually become gefitinib resistant.


OBJECTIVE
In this study, we investigated anti-metastasis effects of bufalin in gefitinib resistant NCI-H460 lung cancer cells.


METHODS
The effects of the bufalin in gefitinib resistant NCI-H460 lung cancer cells were investigated on cell viability using flow cytometry. The adhesion capacity, wound healing assay, invasion and migration assay, and Western blot analysis were used to understand the molecular mechanisms in this study RESULTS: Under sub-lethal concentrations (from 2.5 up to 10nM), bufalin significantly inhibits cell adhension, migration and invasion nature of gefitinib resistant H460 cells. Western blotting assay revealed that bufalin depressed some of the key metastasis-related proteins, such as SOS-1, MMP-2 and Rho A underwent significant reduction. Phosphorylated Focal adhesion kinase (p-FAK), phosphorylated extracellular signal-regulated kinase (p-ERK1/2), Ras and E-cadherin were significantly reduced at 48h treatment. However, phosphorylated p38 (p-p38), phosphorylated c-Jun NH2-terminal kinase (p-JNK1/2) and NF-κBp65 were increased.


CONCLUSIONS
Based on these observations, we suggest that bufalin can be used in anti-metastasis of gefitinib resistant NCI-H460 lung cancer cells in the future.
Department of Nursing, St. Mary's Junior College of Medicine, Nursing and Management, Yilan County, Taiwan.
An-Cheng
AC
Huang
Department of Surgery, China Medical University Hospital, Taichung, Taiwan.
Mei-Due
MD
Yang
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
Yung-Ting
YT
Hsiao
Department of Pharmacy, Saint Mary's Hospital Luodong, Luodong Township, Yilan County, Taiwan.
Tzu-Shun
TS
Lin
School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan; Department of Chinese Medicine, E-Da Hospital, Kaohsiung, Taiwan.
Yi-Shih
YS
Ma
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
Shu-Fen
SF
Peng
Department of Respiratory Therapy, China Medical University, Taichung, Taiwan; Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Te-Chun
TC
Hsia
School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan; Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan.
Yih-Dih
YD
Cheng
Department of Chinese Medicine Resources, China Medical University, Taichung, Taiwan. Electronic address: clclkuo@mail.cmu.edu.tw.
Chao-Lin
CL
Kuo
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan. Electronic address: jgchung@mail.cmu.edu.tw.
Jing-Gung
JG
Chung
D000970:Antineoplastic Agents / Q000494:pharmacology; D002018:Bufanolides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011799:Quinazolines / Q000494:pharmacology*; D020837:SOS1 Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D002018:Bufanolides; D011799:Quinazolines; D020837:SOS1 Protein; C095591:chan su; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020742:rhoA GTP-Binding Protein; D000077156:Gefitinib; C022777:bufalin
Bufalin; Chan Su; Gefitinib resistance; Invasion; Migration; NSCLC