Clinical significance of proliferation, apoptosis and senescence of nasopharyngeal cells by the simultaneously blocking EGF, IGF-1 receptors and Bcl-xl genes.
BACKGROUND
In previous work, we constructed short hairpin RNA (shRNA) expression plasmids that targeted human EGF and IGF-1 receptors messenger RNA, respectively, and demonstrated that these vectors could induce apoptosis of human nasopharyngeal cell lines (CNE2) and inhibit ligand-induced pAkt and pErk activation.


METHODS
We have constructed multiple shRNA expression vectors of targeting EGFR, IGF1R and Bcl-xl, which were transfected to the CNE2 cells. The mRNA expression was assessed by RT-PCR. The growth of the cells, cell cycle progression, apoptosis of the cells, senescent tumor cells and the proteins of EGFR, IGF1R and Bcl-xl were analyzed by MTT, flow cytometry, cytochemical therapy or Western blot.


RESULTS
In group of simultaneously blocking EGFR, IGF1R and Bcl-xl genes, the mRNA of EGFR, IGF1R and Bcl-xl expression was decreased by (66.66±3.42)%, (73.97±2.83)% and (64.79±2.83)%, and the protein expressions was diminished to (67.69±4.02)%, (74.32±2.30)%, and (60.00±3.34)%, respectively. Meanwhile, the cell apoptosis increased by 65.32±0.18%, 65.16±0.25% and 55.47±0.45%, and senescent cells increased by 1.42±0.15%, 2.26±0.15% and 3.22±0.15% in the second, third and fourth day cultures, respectively.


CONCLUSIONS
Simultaneously blocking EGFR, IGF1R and Bcl-xl genes is capable of altering the balance between proliferating versus apoptotic and senescent cells in the favor of both of apoptosis and senescence and, therefore, the tumor cells regression.
Anatomy & Embryology, Wuhan University School of Medicine, Wuhan, Hubei 430071, PR China.
Guodong
G
Dai
Tao
T
Peng
Xuhong
X
Zhou
Jun
J
Zhu
Zhihua
Z
Kong
Li
L
Ma
Zhi
Z
Xiong
Yulin
Y
Yuan
D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000473:pathology* / Q000628:therapy; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000235:genetics
C494811:BCL2L1 protein, human; D051020:bcl-X Protein; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1
Bcl-xl; Epidermal growth factor receptor; Insulin-like growth factor-1 receptor; Nasopharyngeal cancer; Senescence; Short hairpin RNA