Yichao Liu1, Rudolf M Huber1, Rosemarie Kiefl1, Amanda Tufman1, Diego Kauffmann-Guerrero2. 1. Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V and Thoracic Oncology Centre Munich (TOM), University of Munich (LMU), Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Munich, Germany. 2. Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V and Thoracic Oncology Centre Munich (TOM), University of Munich (LMU), Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Munich, Germany Diego.KauffmannGuerrero@med.uni-muenchen.de.
Abstract
BACKGROUND/AIM: Resistance to chemotherapeutic agents is the main cause of reduced survival in non-small cell lung cancer (NSCLC) patients. The Hedgehog (HH) pathway has been shown to be crucial in cell development and survival. Activated in several types of cancer it might be a potent bypass mechanism mediating chemotherapy resistance. MATERIALS AND METHODS: HCC827 NSCLC cells were treated with sub-lethal doses of pemetrexed to produce pemetrexed resistance. RT-qPCR was performed to measure gene expression of HH pathway proteins. A cell growth assay was used to measure the impact of the HH-inhibitor Gant61 in naïve and chemoresistant cell lines. RESULTS: Pemetrexed resistant cells showed significantly increased expression of HH signaling genes (GLI1, GLI2, GLI3, PTCH1, SHH). Supporting these results, pemetrexed resistant cells treated with the HH inhibitor Gant61 showed reduced proliferation compared to naïve cells. CONCLUSION: HH pathway may play an important role in mediating pemetrexed resistance in NSCLC cells. Blocking the HH pathway may be a potential option to overcome this resistance. Copyright
BACKGROUND/AIM: Resistance to chemotherapeutic agents is the main cause of reduced survival in non-small cell lung cancer (NSCLC) patients. The Hedgehog (HH) pathway has been shown to be crucial in cell development and survival. Activated in several types of cancer it might be a potent bypass mechanism mediating chemotherapy resistance. MATERIALS AND METHODS:HCC827 NSCLC cells were treated with sub-lethal doses of pemetrexed to produce pemetrexed resistance. RT-qPCR was performed to measure gene expression of HH pathway proteins. A cell growth assay was used to measure the impact of the HH-inhibitor Gant61 in naïve and chemoresistant cell lines. RESULTS:Pemetrexed resistant cells showed significantly increased expression of HH signaling genes (GLI1, GLI2, GLI3, PTCH1, SHH). Supporting these results, pemetrexed resistant cells treated with the HH inhibitor Gant61 showed reduced proliferation compared to naïve cells. CONCLUSION: HH pathway may play an important role in mediating pemetrexed resistance in NSCLC cells. Blocking the HH pathway may be a potential option to overcome this resistance. Copyright
Authors: Xiaohong Han; Rongrong Luo; Lin Wang; Lei Zhang; Tao Wang; Yan Zhao; Shanshan Xiao; Nan Qiao; Chi Xu; Lieming Ding; Zhishang Zhang; Yuankai Shi Journal: Am J Cancer Res Date: 2020-12-01 Impact factor: 6.166