Effect of verapamil on the expression of EGFR and NM23 in A549 human lung cancer cells.
Despite the advances in the detection and treatment of lung cancer, the overall 5-year survival is only 10-20%. Accumulating evidence suggests that verapamil, a calcium channel antagonist, is a potential anticancer agent. Epidermal growth factor receptor (EGFR) is a key therapeutic target in many types of cancer, whereas nm23 is a putative metastasis suppressor gene. In this study, the effect of verapamil on the expression of nm23 and EGFR in A549 human lung cancer cells was investigated by quantitative real-time reverse transcription-polymerase reaction and immunohistochemical assays. The expression of EGFR and nm23 was also determined in lung cancer patients. Verapamil significantly reduced EGFR expression at both the mRNA and protein levels in A549 cells (p < 0.01). Verapamil also significantly increased the protein levels of nm23 in these cells (p < 0.01), although the mRNA levels of nm23 were not changed after verapamil treatment. Furthermore, the expression of EGFR in human lung cancer tissues was significantly higher than in normal lung tissues (p < 0.001). However, the expression of nm23 was not different between lung cancer and normal tissues. Our data suggest that verapamil may regulate the expression of EGFR and nw23 in lung cancer cells by transcriptional and post-transcriptional levels, respectively. EGFR may be a promising therapeutic molecular target for lung cancer treatment using verapamil and/or chemotherapeutic agents.
Zhang
Chundi
C
Department of Respiratory Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin.
Lv
Fuzhen
F
Zhou
Li
L
Li
Xueyan
X
Wu
Xiu-Xian
XX
Hoffman
Robert M
RM