title: Effect of Fraxiparine, a type of low molecular weight heparin, on the invasion and metastasis of lung adenocarcinoma A549 cells.
abstract: Lung cancer is one of the most highly malignant tumors, and a significant threat to human health. Lung cancer patients often exhibit tumor cell invasion and metastasis, which often render current treatments ineffective. Recently, the beneficial effects of low molecular weight heparin (LMWH) on cancer metastasis were reported in pre-clinical research studies. LMWH may be a potential drug for cancer therapy. However, the mechanism of LMWH on the invasion and metastasis of cancer has yet to be determined. This study investigated the effects of Fraxiparine on the proliferation, invasion and metastasis of the human lung adenocarcinoma A549 cell line. MTT assay and flow cytometry showed that Fraxiparine slightly inhibited the cell viability dose- and time-dependently, but did not arrest the A549 cells in the G1 phase nor induce early apoptosis. The transwell chamber assay showed that Fraxiparine significantly suppressed the invasion and migration of the A549 cells in vitro. Fraxiparine also markedly inhibited the adhesion of the A549 cells to Matrigel. The RT-PCR assay demonstrated that the reduction in invasion and metastasis may be related to the up-regulation of nm23-H1 and the down-regulation of the heparanase expression. Moreover, the RT-PCR assay and Western blot analysis demonstrated that down-regulation of the expression of integrin β1 and β3, as well as that of matrix metalloproteinase-2 and -9 may be responsible for the inhibition of the invasion and metastasis of A549 cells by Fraxiparine.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610041 Sichuan, P.R. China.
authors.forename: Chuan-Jiang
authors.initials: CJ
authors.lastname: Yu
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Ye
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Feng
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Ou
authors.forename: Xi-Kun
authors.initials: XK
authors.lastname: Zhou
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Li
authors.forename: Yong-Qiu
authors.initials: YQ
authors.lastname: Mao
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei