Antitumor activity of kinetochore-associated protein 2 siRNA against lung cancer patient-derived tumor xenografts

It has been widely reported that patient-derived tumor xenografts (PDXs) are more similar to tumor tissues than conventional cancer cell lines. Kinetochore-associated protein 2 (KNTC2) is known to be upregulated specifically in tumor tissues of cancer patients and is recognized as a potential target...

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Bibliographic Details
Published inOncology letters Vol. 15; no. 4; pp. 4676 - 4682
Main Authors Makita, Yukimasa, Teratani, Mika, Murata, Shumpei, Hoashi, Yasutaka, Matsumoto, Satoru, Kawamata, Yuji
Format Journal Article
LanguageEnglish
Published Greece Spandidos Publications 01.04.2018
Spandidos Publications UK Ltd
D.A. Spandidos
Subjects
Cancer therapies
Care and treatment
Cell cycle
Development and progression
Drugs
Gene expression
Genetic aspects
Growth factors
Health aspects
Inhibitor drugs
Kinases
Lipids
Lung cancer
Methods
Nanoparticles
Patient outcomes
Patients
Pharmaceutical industry
Polymerase chain reaction
Proteins
RNA
Targeted cancer therapy
Xenotransplantation
United Kingdom > UK
Japan
lung cancer
three-dimensional culture
patient-derived tumor xenograft
lipid nanoparticle
kinetochore-associated protein 2
erlotinib
short interfering RNA
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Summary:It has been widely reported that patient-derived tumor xenografts (PDXs) are more similar to tumor tissues than conventional cancer cell lines. Kinetochore-associated protein 2 (KNTC2) is known to be upregulated specifically in tumor tissues of cancer patients and is recognized as a potential target for cancer therapy. Previously, antitumor activities of KNTC2 short interfering RNA encapsulated into a lipid nanoparticle (KNTC2-LNP) were reported in orthotopic hepatocellular carcinoma mouse models. However, it remains unclear whether KNTC2-LNP exhibits antitumor activities against lung cancer PDXs. In the present study, the antitumor activities of KNTC2-LNP were clarified in a three-dimensional culture system and a subcutaneous tumor model of lung cancer PDX, LC-60, which was resistant to erlotinib. Growth inhibitory activities of KNTC2-LNP were associated with knockdown activities. Furthermore, KNTC2-LNP also exhibited antitumor activity against another lung cancer PDX, LC-45, which was sensitive to erlotinib. These results suggest that KNTC2 is a promising target for patients with lung cancer.
ISSN:1792-1074
1792-1082
DOI:10.3892/ol.2018.7890