Open Access
ARTICLE
MiR-21/Sonic Hedgehog (SHH)/PI3K/AKT Pathway is Associated with NSCLC of Primary EGFR-TKI Resistance
Li Xu, Kang Li, Jia Li, Liyu Liu, Fang Xu, Yan Xu, Yi Kong, Xingxiang Pu, Qianzhi Wang, Jingyi Wang, Bolin Chen*, Lin Wu*
The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of
Medicine, Central South University, Changsha, 410013, China
* Corresponding Authors: Bolin Chen. Email: ; Lin Wu. Email:
Oncologie 2022, 24(3), 579-590. https://doi.org/10.32604/oncologie.2022.022121
Received 22 February 2022; Accepted 11 July 2022; Issue published 19 September 2022
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.
Keywords
Cite This Article
Xu, L., Li, K., Li, J., Liu, L., Xu, F. et al. (2022). MiR-21/Sonic Hedgehog (SHH)/PI3K/AKT Pathway is Associated with NSCLC of Primary EGFR-TKI Resistance.
Oncologie, 24(3), 579–590.