Hedgehog Pathway Activation Might Mediate Pemetrexed Resistance in NSCLC Cells

Anticancer Research
Yichao LiuD Kauffmann-Guerrero

Abstract

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. 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. 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. 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.

Citations

Feb 21, 2021·Archives of Pharmacal Research·Hye-Young Min, Ho-Young Lee
May 11, 2021·Frontiers in Cell and Developmental Biology·Vivek KumarB S Dwarakanath

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