Abstract 2380: Curcumin reduces pulmonary tumorigenesis in vascular endothelial growth factor (VEGF)-overexpressing transgenic mice
Authors: Tung Yu-Tang , Chen Hsiao-Ling , Tsai Tung-Chou , Lai Cheng-Wei , Shen Chih-Jie , Lai Yi-Wen , Chen Chuan-Mu 
Published: June 2012

Transgenic animal techniques that provide animal models of human cancers have been widely used in biomedical research. Pulmonary cancers are among the most common cancers in the world. Angiogenesis is an important factor in the formation of tumors, tumor growth, invasion, and metastases. The vascular endothelial growth factor promotes the initial formation of blood vessels (vasculogenesis) and plays a vital role in the growth and expansion of existing blood vessels (angiogenesis). The study is to provide a method for manufacturing an animal model for researching a pulmonary tumor and serve as an animal model for researching the regulatory mechanism of the pulmonary adenocarcinoma. We investigated an lung-specific hVEGF-A165 overexpressed transgenic mice model which constructed mccsp-Vegf-A165-sv40 poly(A) transgene. The results showed that hVegf-A165 mRNA can be expressed specifically in the lung tissue of the transgenic mice. In the histopathologic slides of the lung tissue, it seemed that hVEGF-A165 overexpressed transgenic mice can induce bronchial epithelium flattened, abnormalproliferation of cells on bronchial epithelium, inflammation, fibrosis, adenoma, and cyst in the transgenic mice. In pathological section, we referred specimen to different levels of lung lesion, which showed a positive correlation with the expression levels of hVEGF by IHC, PCR, and western blot. Moreover, we performed cDNA microarray to exam gene expressions on lung samples of transgenic mice. The relative gene clusters of cell proliferation, cell cycle, cell metastasis, carcinogenesis, and angiogenesis were chosen to evaluate by RT-PCR, Q-PCR, and Western blots.

Curcumin is a major active polyphenol compound of turmeric and exhibits remarkable effects on cancers such as brain, colon, bladder, breast, prostate and cervical cancers. In this study, we found that curcumin significantly eliminated hVEGF-A165 overexpression to normal, specifically in clara cells of the lungs of transgenic mice, and suppressed the formation of tumors. In addition, we demonstrated a relationship between curcumin treatment and the expression of VEGF, EGFR, ERK2, and Cyclin A at the transcriptional and translational levels. We also noticed a reduction of Cyclin A and Cyclin B treatment with curcumin that was an effect on the cell cycle. Curcumin-induced inhibition of Cyclin A and Cyclin B likely results in decreased progression through the S and G2/M phases. These results demonstrated that the expression of proteins involved in the S to M phase transition in transgenic mice is suppressed by curcumin. This result suggests that a blockade of the cell cycle may be a critical mechanism for the observed effects on vasculogenesis and angiogenesis following treatment with curcumin. This study additionally provides an animal model for analyzing the mechanisms of the regulation and proliferation of pulmonary adenocarcinoma.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2380. doi:10.1158/1538-7445.AM2011-2380