Effects of lentivirus-mediated silencing of Periostin on tumor microenvironment and bone metastasis via the integrin-signaling pathway in lung cancer

Autor: Jing Che, Xianglin Yuan, Peng Zhang, Yong-De Liao, Wen-Zhuang Shen, Yu-Hong Dai, Yu Deng
Rok vydání: 2016
Předmět:
0301 basic medicine
Adult
Male
Lung Neoplasms
Down-Regulation
Mice
Nude
Bone Neoplasms
Enzyme-Linked Immunosorbent Assay
Periostin
Transfection
General Biochemistry
Genetics and Molecular Biology
Metastasis
03 medical and health sciences
Mice
Young Adult
0302 clinical medicine
Nude mouse
Cell Movement
medicine
Tumor Microenvironment
Gene silencing
Animals
Humans
Gene Silencing
RNA
Messenger
General Pharmacology
Toxicology and Pharmaceutics
RNA
Small Interfering
Aged
Cell Proliferation
Integrin Signaling Pathway
Tumor microenvironment
Mice
Inbred BALB C
biology
Lentivirus
Bone metastasis
General Medicine
Middle Aged
medicine.disease
biology.organism_classification
Integrin alphaVbeta3
Molecular biology
Gene Expression Regulation
Neoplastic
030104 developmental biology
030220 oncology & carcinogenesis
Case-Control Studies
Female
Cell Adhesion Molecules
Signal Transduction
Zdroj: Life sciences. 182
ISSN: 1879-0631
Popis: The study aims to investigate the effects of Periostin gene silencing on tumor microenvironment and bone metastasis via the integrin-signaling pathway in lung cancer (LC). LC patients were divided into bone metastasis and non-bone metastasis groups; Healthy volunteers were selected as normal group. ELISA was performed to detect serum Periostin levels and plasma calcium ion concentration. SBC-5 cells were assigned into blank group (without transfection), negative control (NC) group (transfected with empty plasmid), si-Periostin group (transfected with si-Periostin plasmid), si-Integrin-αvβ3 group (transfected with Integrin-αvβ3 siRNA plasmid) and si-Periostin+si-Integrin-αvβ3 group (transfected with si-Periostin and si-Integrin-αvβ3 plasmid). qRT-PCR and Western blotting were performed to determine mRNA and protein expression of Periostin, metastasis-associated factors of tumor microenvironment and integrin signaling pathway-related proteins. CCK-8, scratch test and transwell assay were applied to detect cell proliferation, migration and invasion respectively. Nude mouse models of LC bone metastasis were established. TRAP Staining was employed to measure the number of osteoclasts. Bone metastasis group exhibited higher levels of Periostin compared to normal and non-bone metastasis groups. Si-Periostin, si-Integrin-αvβ3 and si-Periostin+si-Integrin-αvβ3 groups showed decreased Periostin expression, proliferation rate, migration distance, invasive cells, and expressions of metastasis-associated factors of tumor microenvironment and integrin signaling pathway-related proteins compared to blank and NC groups. Similarly, number of osteoclasts and expression of integrin signaling pathway-related proteins were decreased, and bone injury and calcium ion concentration were reduced. The study demonstrated that down-regulation of Periostin expression modulated tumor microenvironment and inhibited bone metastasis by blocking integrin-signaling pathway in LC.
Databáze: OpenAIRE
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