Objective:To investigate the effect of afatinib, a tyrosine kinase inhibitor, on the proliferation, cell cycle, and apoptosis of human breast cell lines, and compare its effects with those of gefitinib. Methods:Three human breast cell lines, MCF-7, T47D, and MDA-MB-231, were cultured as cell models. A methyl thiazolyl tetrazolium assay was utilized to measure cell viability. Flow cytometer was used to analyze the cell cycle arrest (PI staining) and apoptosis rates (Annexin-V/PI staining). The protein expression was detected by Western blot analysis. Results:The proliferation of three human breast cell lines was significantly inhibited by afatinib, and the IC50 levels of MCF-7, T47D, and MDA-MB-231 were 0.101, 0.141, and 0.887μmol/L, respectively. The G0/G1 phase cell ratio increased con-siderably 24 h after afatinib was added to T47D or MDA-MB-231. The cell apoptosis rate also increased in the two cell lines (88.9%and 58.1%). The cleavage of apoptosis pathway proteins PARP and caspase-3 was also promoted by afatinib. Phosphorylation of EGFR was significantly inhibited by afatinib in the MDA-MB-231 cell line. Finally, the inhibition effect of afatinib was stronger than that of gefi-tinib. Conclusion: Afatinib could significantly inhibit the proliferation of breast cancer cells and promote apoptosis. The effect was dose-dependent. Afatinib was a more effective tyrosine kinase inhibitor as compared with gefitinib.

Objective To investigate the effects of a new c-Met inhibitor SU11274 on apoptosis and motility of c-Met-positive basal-like breast cancer cells MDA-MB-231. Methods The concentrations of SUl1274 were set to 0,0.1,1,10 and 20 μmol/L.Morphological change of apoptotic cells was analyzed by Hoechst33342,MitroTrackerRed and Yo-pro-1 staining.The apoptotic rate of MDA-MB-231 cells were determined by Annexin V/PI double-staining. The expression of apoptosis related proteins (Bcl-XL,Caspase-3 and PARP) and phosphorylation levels of c-Met and Akt were analyzed by Western blot.The capability of motility were measured by wound-healing assay and chemotaxis assay. Results After treatment by SU11274( 10 μmol/L) for 48 h,shrinking apoptotic cells of MDA-MB-231 was observed by flurescent microscope and nuclear fragmentation was seen.Annexin V/PI double-staining showed SU11274induced apoptosis of MDA-MB-231 cells (P ＜ 0.05 ),and the apoptotic rates were (7.3 ± 0.9) ％,( 14.1 ±0.6) ％,(35.5 ± 4.4) ％ and (48.2 ± 5.3 ) ％,respectively.SU11274 downregulated the expression of Bcl-XL and promoted the dissection of Caspase-3 and PARP in a dose dependent relationship.SU11274 prolongs the wound-healing time,decreases the migration cell count (P ＜ 0.05 ) and effectively inhibits the phosphorylation of c-Met and its downstream key proteins Akt in a dose-dependent manner.Conclusions C-Met inhibitor SU11274 induces apoptosis and inhibits the motility of c-Met-positive basallike breast cancer cell line MDA-MB-231,probably through inhibiting phosphorylation of c-Met/PI3K/Akt.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in China. Radiotherapy is the first-line treatment. After appropriate radiotherapy, about 5%-15% patients experience recurrence. In view of the poor efficacy and high incidence of severe late toxicities associated with re-irradiation, salvage surgery by the transnasal endoscopic approach is recommended for recurrent NPC (rNPC). Compared with re-irradiation, endoscopic surgery can better prolong survival, improve the quality of life, and reduce complications and medical expenses of patients with rNPC. However, the complexity of the nasopharyngeal skull base enhances the difficulty and risk of surgery. Expanding the boundary of surgical resection remains a clinical challenge for otolaryngologists. In this regard, to help more advanced patients with rNPC, the surgical innovative system of NPC needs to be established by multi-disciplinary cooperation, involving skull base anatomy-based investigation, appropriate administration of the internal carotid artery (ICA), repair of skull base defect, and establishment of various types of endoscopic endonasal nasopharyngectomy.