A Novel Strategy to Improve the Therapeutic Efficacy of Gemcitabine for Non-Small Cell Lung Cancer by the Tumor-Penetrating Peptide iRGD.

A Novel Strategy to Improve the Therapeutic Efficacy of Gemcitabine for Non-Small Cell Lung Cancer by the Tumor-Penetrating Peptide iRGD.
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DOI:
10.1371/journal.pone.0129865
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Zheng J
Zheng J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang Q;Zhang Y;Li K;Wang H;Li H;Zheng J

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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.
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