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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimetabolites, Antineoplastic / administration & dosage
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Antimetabolites, Antineoplastic / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Apoptosis
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Cell Line, Tumor
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Deoxycytidine / administration & dosage
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / therapeutic use
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Female
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Gemcitabine
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Humans
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Mice
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Mice, Inbred BALB C
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Oligopeptides / administration & dosage
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Oligopeptides / therapeutic use*
Substances
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Antimetabolites, Antineoplastic
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Oligopeptides
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Deoxycytidine
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arginyl-glycyl-aspartic acid
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Gemcitabine
Grants and funding
This work was supported by Natural Science Foundation of Jiangsu Province (BK2012146,
http://www.jstd.gov.cn/), National Natural Science Foundation of China (81301946,
http://www.nsfc.gov.cn/), Jiangsu Provincial Office of Education Foundation (JHB2012-34,
http://www.ec.js.edu.cn/), China Postdoctoral Science Foundation funded project (2013M540467,
http://res.chinapostdoctor.org.cn/BshWeb/index.shtml), and Xuzhou Medical College Foundation (2012KJZ23,
http://www.xzmc.edu.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.