Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent antitumor activity against human lung cancer in vivo.
Lung cancer is one of the leading causes of death in the world. The underlying cause for lung cancer has been attributed to various factors that include alteration and mutation in the tumor suppressor genes. Restoration of normal function of the tumor suppressor gene is a potential therapeutic strategy. Recent studies have identified a group of candidate tumor suppressor genes on human chromosome 3p21.3 that are frequently deleted in human lung and breast cancers. Among the various genes identified in the 3p21.3 region, we tested the antitumor activity of the FUS1 gene in two human non-small-cell lung cancer (NSCLC) xenografts in vivo. Intratumoral administration of FUS1 gene complexed to DOTAP:cholesterol (DOTAP:Chol) liposome into subcutaneous H1299 and A549 lung tumor xenograft resulted in significant (P = .02) inhibition of tumor growth. Furthermore, intravenous injections of DOTAP:Chol-FUS1 complex into mice bearing experimental A549 lung metastasis demonstrated significant (P = .001) decrease in the number of metastatic tumor nodules. Finally, lung tumor-bearing animals when treated with DOTAP:Chol-FUS1 complex demonstrate prolonged survival (median survival time: 80 days, P = .01) compared to control animals. This result demonstrates the potent tumor suppressive activity of the FUS1 gene and is a promising therapeutic agent for treatment of primary and disseminated human lung cancer.
Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Isao
I
Ito
Lin
L
Ji
Fumihiro
F
Tanaka
Yuji
Y
Saito
Began
B
Gopalan
Cynthia D
CD
Branch
Kai
K
Xu
E Neely
EN
Atkinson
Benjamin N
BN
Bekele
L Clifton
LC
Stephens
John D
JD
Minna
Jack A
JA
Roth
Rajagopal
R
Ramesh
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002893:Chromosomes, Human, Pair 3; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D008081:Liposomes; C499993:TUSC2 protein, human; D025521:Tumor Suppressor Proteins