Hua Shen1, Dan Guan1, Jianxin Shen2, Min Wang3, Xiaofeng Chen1, Tongpeng Xu1, Lianke Liu4, Yongqian Shu5. 1. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. 2. Department of Clinical Laborotory, First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei Province, China. 3. Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. 4. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. Electronic address: liulianke@medmail.com.cn. 5. Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. Electronic address: shuyongqian1999@126.com.
Abstract
BACKGROUND: TKI-acquired resistance is a tough obstacle for effectively treating NSCLC patients with EGFR mutant characteristics. T790M mutations and MET amplifications account for 70% of the acquired resistance, but the causes for the remaining 30% need elucidation. METHODS: We detected TGF-β1and PTEN expression levels in 51 NSCLC patients undergoing EGFR-TKI treatment using Immunohistochemistry (IHC) assay. We examined erlotinib sensitivity, apoptosis rate, and invasion ability in PC-9 cells and PC-9/TGF-β1 cells with CCK-8, flow cytometry, and trans-well assays. We examined and analyzed the AKT and ERK pathways' expression levels using western blot. RESULTS: High TGF-β1 and low PTEN expression levels were correlated with poor EGFR-TKI sensitivity and overall survival in 51 NSCLC samples. In vitro analysis revealed that TGF-β1 could reduce erlotinib sensitivity, increase anti-apoptosis ability and invasive characteristic in TKI-sensitive PC-9 cell lines by down-regulating PTEN and activating the Akt and ERK pathways. CONCLUSIONS: The results suggest that TGF-β1 demonstrated another acquired erlotinib resistance by down-regulating PTEN expression.
BACKGROUND: TKI-acquired resistance is a tough obstacle for effectively treating NSCLCpatients with EGFR mutant characteristics. T790M mutations and MET amplifications account for 70% of the acquired resistance, but the causes for the remaining 30% need elucidation. METHODS: We detected TGF-β1and PTEN expression levels in 51 NSCLCpatients undergoing EGFR-TKI treatment using Immunohistochemistry (IHC) assay. We examined erlotinib sensitivity, apoptosis rate, and invasion ability in PC-9 cells and PC-9/TGF-β1 cells with CCK-8, flow cytometry, and trans-well assays. We examined and analyzed the AKT and ERK pathways' expression levels using western blot. RESULTS: High TGF-β1 and low PTEN expression levels were correlated with poor EGFR-TKI sensitivity and overall survival in 51 NSCLC samples. In vitro analysis revealed that TGF-β1 could reduce erlotinib sensitivity, increase anti-apoptosis ability and invasive characteristic in TKI-sensitive PC-9 cell lines by down-regulating PTEN and activating the Akt and ERK pathways. CONCLUSIONS: The results suggest that TGF-β1 demonstrated another acquired erlotinib resistance by down-regulating PTEN expression.
Authors: Chaoyuan Liu; Luxi Qian; Karin A Vallega; Guangzhi Ma; Dan Zong; Luxiao Chen; Shaomeng Wang; Suresh R Ramalingam; Zhaohui Qin; Shi-Yong Sun Journal: Am J Cancer Res Date: 2022-02-15 Impact factor: 6.166