title: A Novel Strategy to Improve the Therapeutic Efficacy of Gemcitabine for Non-Small Cell Lung Cancer by the Tumor-Penetrating Peptide iRGD.
abstract: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, comprising approximately 75-80% of all lung cancers. Gemcitabine is an approved chemotherapy drug for NSCLC. The objective of this study was to develop a novel strategy to improve the therapeutic efficacy of Gemcitabine for NSCLC by the co-administered iRGD peptide. We showed that the rates of positive expression of αvβ3, αvβ5 and NRP-1 in the A549 cell line were 68.5%, 35.3% and 94.5%, respectively. The amount of Evans Blue accumulated in the tumor of Evans Blue+iRGD group was 2.5 times that of Evans Blue group. The rates of growth inhibition of the tumors of the iRGD group, the Gemcitabine group and the Gemcitabine+iRGD group were 8%, 59.8% and 86.9%, respectively. The results of mechanism studies showed that PCNA expression in the Gemcitabine+iRGD group decreased 71.5% compared with that in Gemcitabine group. The rate of apoptosis in the Gemcitabine+iRGD group was 2.2 time that of the Gemcitabine group. Therefore, the tumor-penetrating Peptide iRGD can enhance the tumor-penetrating ability and therapeutic efficacy of Gemcitabine in the A549 xenograft. The combined application of Gemcitabine with iRGD may be a novel strategy to enhance the clinical therapeutic efficacy of Gemcitabine in patients with NSCLC.
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China; Department of Oncology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, 221009, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Li
authors.affiliation: Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, Jiangsu, 221002, China.
authors.forename: Junnian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D009842:Oligopeptides; D003841:Deoxycytidine; C047981:arginyl-glycyl-aspartic acid; D000093542:Gemcitabine