MiR-21/Sonic Hedgehog (SHH)/PI3K/AKT Pathway is Associated with NSCLC of Primary EGFR-TKI Resistance

Abstract

Background: Non-small cell lung cancer (NSCLC), caused by abnormal gene drive, may have primary drug resistance after treatment with tyrosine kinase inhibitors (EGFR-TKIs). Therefore, we explore whether the primary drug-resistant NSCLC treated with EGFR-TKI is related to the miR-21/Sonic Hedgehog (SHH)/PI3K/AKT pathway. Methods: The patients from our hospital who meet the AJCC TNM staging (7th edition) stage IIIB and stage IV NSCLC were selected in this case study. Thereafter, the treatment response of EGFR-TKIs was evaluated according to the solid tumor efficacy evaluation standard (version 1.1). The patients were divided into the EGFR-TKIs primary drug resistance group (EGFR-TKIs-Primary-R) and the EGFR-TKIs sensitive group (EGFR-TKIs-Primary-S). Apoptosis level and degree of fibrosis in patients’ tumor tissues were detected by the TUNEL assay and Masson staining, respectively. The levels of miR-21 and GLI1 were measured by qRT-PCR technique. The contents of E-cadherin and Snail were detected by IF method, and the degree of PI3K/AKT phosphorylation was measured using IHC technique. Results: Compared with the EGFR-TKIs-Primary-S group, the EGFR-TKIs-Primary-R group showed lower levels of apoptosis and tumor tissue fibrosis. The levels of miR-21, GLI1, Snail, p-PI3K and p-AKT increased, while the level of E-cadherin decreased. However, the levels of total protein PI3K and AKT remained the same. Conclusion: NSCLC of primary EGFR-TKI resistance was found to be related to miR-21/SHH, the process of epithelial to mesenchymal transition (EMT), and PI3K/AKT phosphorylation. The present study provides a reference for future research in drug resistance, and paves the way to discover new therapeutic gene targets to alleviate lung cancer drug resistance.