Trichostatin A reverses the chemoresistance of lung cancer with high IGFBP2 expression through enhancing autophagy

• Published in: Scientific reports Vol. 8; no. 1; pp. 3917 - 10
• Main Authors: Tang, Dongfang, Yao, Ruyong, Zhao, Dandan, Zhou, Lin, Wu, Yun, Yang, Yang, Sun, Yifeng, Lu, Liming, Gao, Wen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.03.2018; Nature Publishing Group
• Subjects: 13/1; 13/109; 13/31; 14/63; 38/77; 631/67/1059/2326; 631/67/1612/1350; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Autophagy; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Case-Control Studies; Chemoresistance; Drug Resistance, Neoplasm; Epidermal growth factor receptors; Female; Histone Deacetylase Inhibitors - pharmacology; Histopathology; Humanities and Social Sciences; Humans; Hydroxamic Acids - pharmacology; Insulin; Insulin-Like Growth Factor Binding Protein 2 - metabolism; Insulin-like growth factor-binding protein 2; Insulin-like growth factors; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Metastases; Middle Aged; multidisciplinary; Multivariate analysis; Phagocytosis; Prognosis; Pulmonary lesions; Retrospective Studies; Science; Science (multidisciplinary); Smoking; Surgery; Survival Rate; Trichostatin A; Tumor Cells, Cultured; Tumorigenesis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-22257-1

Insulin-like growth factor (IGF) signaling plays an important role in tumorigenesis and metastasis. Here, we analyzed insulin-like growth factor (IGF) binding protein-2 (IGFBP2) expression in 81 lung cancer patients and 36 controls consisting of healthy and benign pulmonary lesion participants for comparison, then validated the IGFBP2 expression in additional 84 lung cancer patients, and evaluated the prognostic and chemoresistant significance of IGFBP2 in two cohorts respectively. Next we detected the reversal effect of trichostatin A (TSA) on chemoresistance in cell lines with high IGFBP2 expression. As a result, the mean expression of IGFBP2 in lung cancer patients was significantly higher than that in controls and increased with lung cancer progressed to advanced stage. In addition, high IGFBP2 expression was independently predictive for chemoresistance; over-expressed IGFBP2 enhances cell activity and TSA can reverse the chemoresistance induced by high IGFBP2 expression through enhancing autophagy. Furthermore, multivariate analysis showed that lung cancer patients whose blood IGFBP2 was higher had a poor survival outcome, with a hazard ratio of 8.22 (95%CI 1.78–37.92, P = 0.007) after adjustment for stage, histopathology, EGFR mutation, age, smoking and surgery.