Inhibitory effect of adenovirus-uteroglobin transduction on the growth of lung cancer cell lines

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Abstract
Uteroglobin is a secretory protein synthesized by most epithelia, including the respiratory tract. It has strong anti-inflammatory properties that appear to be related to the inhibition of phospholipase A2. Recent experimental evidence indicates that uteroglobin has an inhibitory effect on the proliferation and invasion of cancer cells. We investigated the effects of the adenovirus-uteroglobin (ad-UG) transduction on the growth of lung cancer cell lines, which did not express the uteroglobin gene. Upon transduction of ad-UG, the rate of cell growth and the ability to produce colonies in soft agar were evaluated. Cell cycle analysis, Western blot for cell cycle-related proteins and annexin V staining for apoptosis were carried out to see if they were associated with the changes in cell growth. All the tested lung cancer cell lines did not express the uteroglobin gene. The growth rates, and colony-forming ability of transformed cells, were significantly inhibited by the induction of uteroglobin gene expression. The DNA histogram showed that the cell fraction of the G2/M phase was increased, and this G2/M phase arrest was related to a decrease of cdk1 and cyclin A. However, a fraction of apoptotic cells were same as the control. From these results, uteroglobin is thought to have an inhibitory effect on the growth of lung cancer cells. This suggests a potential role for uteroglobin in gene therapy for lung cancer.