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. Method: 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 MU, 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. (C) 2013 Published by Elsevier Inc.