Abstract: Animal Experiment of Primary Resistance to Gefitinib by Novel AnticancerAgentHong NI, Mao YANG, Zhaohui ZOU, Zhi GUOCorrespondence to: Zhi GUO, E-mail: wnihong@yahoo.com.cnDepartment of Interventional Radiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, ChinaStomatological Hospital of Tianjin Medical University, Tianjin 300070, ChinaThis study was supported by a grant from Tianjin Natural Science Foundation (Grant no. 10JCYBJC25600)Abstract Objective: To study whether the recently identified novel anticancer agent NSC-741909 can suppress the growth of aprimary gefitinib-resistant xenograft mouse model and determine its molecular mechanisms. Methods: H322 ( K-Ras wild, gefi-tinib-sensitive ) and A549 ( K-Ras mutated, gefitinib-resistant ) human tumor xenografts were established and intraperitoneally treatedwith NSC-741909. The growth suppression effect of NSC-741909 on the model was observed and the tumor was resected for further ex-amination. Apoptosis was detected and K-ras, JNK, p-JNK, and MKP1 protein expression was observed byWestern blot analysis and re-verse transcription polymerase chain reaction. Results: NSC-741909 can suppress the growth of primary gefitinib-resistant xenograftsin a mouse model. NSC-741909 can induce apoptosis. Mutated K-ras and MKP1 expression were suppressed. P-JNK was activated,whereas total JNK protein expression was unchanged. NSC-741909 had little effect on the H322 mouse model. Conclusion:NSC-741909 can suppress the growth of primary gefitinib-resistant xenografts and induce apoptosis in a mouse model. This inhibitionis mediated by sustained JNK activation.Keywords K-ras mutation; NSCLC; Gefitinib primary resistance