Knockdown of Importin 7 Inhibits Lung Tumorigenesis in K-rasLA1 Lung Cancer Mice

Ah Young Lee; Sangwha Kim; Somin Lee; Hu-Lin Jiang; Sang-Bum Kim; Seong-Ho Hong; Myung-Haing Cho

doi:10.21873/anticanres.11576

Knockdown of Importin 7 Inhibits Lung Tumorigenesis in K-ras^LA1 Lung Cancer Mice

Anticancer Res. 2017 May;37(5):2381-2386. doi: 10.21873/anticanres.11576.

Authors

Ah Young Lee¹, Sangwha Kim^{1

2}, Somin Lee^{1

2}, Hu-Lin Jiang³, Sang-Bum Kim⁴, Seong-Ho Hong^{5

4}, Myung-Haing Cho^{5

2

6

7

8}

Affiliations

¹ Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
² Graduate Group of Tumor Biology, Seoul National University, Seoul, Republic of Korea.
³ State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P.R. China.
⁴ New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea.
⁵ Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea duck1240@naver.com mchotox@snu.ac.kr.
⁶ Department of Nano Fusion Technology, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea.
⁷ Advanced Institute of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
⁸ Institute of GreenBio Science Technology, Seoul National University, Daehwa-myeon, Republic of Korea.

PMID: 28476804
DOI: 10.21873/anticanres.11576

Abstract

Background/Aim: Lung cancer shows the highest estimated deaths in both males and females in the Unites States. Importin 7 is overexpressed in lung adenocarcinoma tissues. In this study, we aimed to demonstrate the anticancer effect of importin 7 down-regulation, especially in lung cancer. Materials and Methods: Glycerol propoxylate triacrylate spermine (GPT-SPE) is a biocompatible carrier used for aerosol gene delivery. Repeated aerosol delivery of GPT-SPE/shImportin 7 complexes was performed to 10-week-old male K-ras^LA1mice (a murine lung cancer model) twice a week for 4 weeks (8 times) in a nose-only exposure chamber. Results: Aerosol delivery of GPT-SPE/shImportin 7 inhibits lung cancer in K-ras^LA1mice compared to control and scramble control groups. Moreover, importin 7-down-regulated stable cell-line demonstrates suppression of proliferation through Akt inhibition and apoptosis. Conclusion: Down-regulation of importin 7 significantly suppresses lung cancer in vitro and in vivo.

Keywords: GPT-SPE; Lung cancer; aerosol delivery; gene therapy; importin 7.

MeSH terms

Adenocarcinoma / metabolism*
Adenocarcinoma / pathology
Adenocarcinoma of Lung
Animals
Apoptosis
Carcinogenesis
Cell Line, Tumor
Down-Regulation
Gene Knockdown Techniques
Gene Transfer Techniques
Humans
Karyopherins / genetics*
Karyopherins / metabolism
Lung / metabolism
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology
Male
Mice, Inbred C57BL
Mice, Transgenic
Poly(ADP-ribose) Polymerases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins p21(ras) / genetics
RNA, Small Interfering / genetics
Tumor Suppressor Protein p53 / metabolism
bcl-2-Associated X Protein / metabolism
bcl-X Protein / metabolism

Substances

Bax protein, mouse
Bcl2l1 protein, mouse
Karyopherins
RNA, Small Interfering
Tumor Suppressor Protein p53
bcl-2-Associated X Protein
bcl-X Protein
Ipo7 protein, mouse
Poly(ADP-ribose) Polymerases
Proto-Oncogene Proteins c-akt
Hras protein, mouse
Proto-Oncogene Proteins p21(ras)