Peptidomic analysis of pilose antler and its inhibitory effect on triple-negative breast cancer at multiple sites
FOOD & FUNCTION
Authors: Zheng, Kexin; Li, Qilong; Lin, Dongdon; Zong, Xiaoyan; Luo, Xue; Yang, Mei; Yue, Xiqing; Ma, Shiliang
Abstract
Pilose antler (PA) is a traditional Chinese functional food that has been reported to inhibit breast cancer; however, the specific substances that exert this effect and the underlying mechanisms remain unknown. This study aims to identify the specific proteins in PA water-soluble polypeptides (PAWPs) that are involved in cancer inhibition and determine the effects of PAWPs on triple-negative breast cancer in mice. In this study, peptidomic analysis of 105 varieties of polypeptides from PAWPs was carried out using LC-MS, 22 of which had functions that could potentially suppress tumors, including endopeptidase inhibitors, metal ion-binding proteins, angiogenesis inhibitors, intercellular adhesion proteins, and extracellular matrix repair proteins. Furthermore, we showed that intragastric administration of PAWPs into mice inhibited the growth and metastasis of triple-negative 4T1 breast tumors. PAWPs activated the expression of cleaved-caspase3 and increased tumor apoptosis, resulting in the reduction of platelet-endothelial cell adhesion molecule (PECAM-1/CD31) expression and the number of blood vessels, as well as the inhibition of matrix metalloproteinase (MMP) 2 and 9, increasing the ratio of Cadherin-1 (CDH1)/Cadherin-2 (CDH2) and inhibiting epithelial-mesenchymal transition (EMT) in these tumors. Therefore, PAWPs inhibit the progression and metastasis of triple-negative 4T1 breast cancer at multiple key sites in mice and contain various tumor suppressor proteins that are potentially involved in these processes.
Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro
CHINESE MEDICAL JOURNAL
Authors: Xu Qing-yong; Gao Yuan; Liu Yan; Yang Wei-zhi; Xu Xiang-ying
Abstract
Background Radiotherapy plays a critical role in the management of non-small cell lung cancer (NSCLC). This study was conducted to identify gene expression profiles of acquired radioresistant NSCLC cell line established by fractionated ionizing radiation (FIR) by cDNA microarray. Methods The human lung adenocarcinoma cell line Anip973 was treated with high energy X-ray to receive 60 Gy in 4 Gy fractions. The radiosensitivity of Anip973R and its parental line were measured by clonogenic assay. Gene expression profiles of Anip973R and its parental line were analyzed using cDNA microarray consisting of 21 522 human genes. Identified partly different expressive genes were validated by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). Results Fifty-nine upregulated and 43 downregulated genes were identified to radio-resistant Anip973R. Up-regulated genes were associated with DNA damage repair (DDB2), extracellular matrix (LOX), cell adhesion (CDH2), and apoptosis (CRYAB). Down-regulated genes were associated with angiogenesis (GBP-1), immune response (CD83), and calcium signaling pathway (TNNC1). Subsequent validation of selected eleven genes (CD24, DDB2, IGFBP3, LOX, CDH2, CRYAB, PROCR, ANXA1 DCN, GBP-1 and CD83) by Q-RT-PCR was consistent with microarray analysis. Conclusions Fractionated ionizing radiation can lead to the development of radiation resistance. Altered gene profiles of radioresistant cell line may provide new insights into mechanisms underlying clinical radioresistance for NSCLC.