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S100A6 诱导具有 EGFR 19 外显子突变的人肺腺癌 PC9 细胞系对吉非替尼产生耐药性

 

Authors Wang T , Shou X

Received 10 April 2025

Accepted for publication 23 September 2025

Published 29 September 2025 Volume 2025:17 Pages 2235—2244

DOI https://doi.org/10.2147/CMAR.S533644

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li

Ting Wang,1 Xiaoai Shou2 

1Department of Respiratory Medicine, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, 710004, People’s Republic of China; 2Department of Pharmacy, Xi’an People’s Hospital (Xi’an Fourth Hospital), Xi’an, 710004, People’s Republic of China

Correspondence: Xiaoai Shou, Department of Pharmacy, Xi’an People’s hospital (Xi’an Fourth Hospital), Xi’an, 710004, People’s Republic of China, Tel/Fax +86-15829327671, Email sxa1988@163.com

Introduction: S100 calcium binding protein A6 (S100A6) has been confirmed to be involved in the occurrence and development of various malignant tumors, including lung adenocarcinoma (LADC). The impact of S100A6 on the drug resistance of cancer cell lines is still uncovered. PC9 cells with EGFR 19 exon mutation is commonly used in lung cancer cell experiments.
Methods: In this work, PC9 cells over-expressing S100A6 (PC9/S100A6) was successfully constructed, and the PC9 cells were set as control group simultaneously. MTT assay was used to detect and compare the growth rates of the cells in two groups at different concentrations and time points of gefitinib, cisplatin, pemetrexed, bevacizumab.
Results: Data showed that the inhibitory rates of gefitinib (0.01μmol/L, 0.1μmol/L, 1μmol/L) on PC9/S100A6 cells significantly decreased at 24h, 48h, 72h (P< 0.05). Additionally, the inhibitory effects on PC9/S100A6 cells were significantly lower for 10 μmol/L gefitinib (at 48h and 72h), 100 μmol/L gefitinib (at 72h), 2.5 μg/mL cisplatin (at 48h and 72h), and 10 μg/mL cisplatin (at 72h). However, there is no obvious difference in the inhibitory rate of cisplatin (2.5μg/mL 24h; 10μg/mL 24h, 48h; 5μg/mL, 20μg/mL, 40μg/mL 24h, 48h, and 72h), pemetrexed, bevacizumab on two groups.
Conclusion: Our results demonstrated that S100A6 can apparently promote the resistance to gefitinib of LADC PC9 cell lines with EGFR 19 exon mutations.

Keywords: S100A6, EGFR 19 exon mutation, PC9, gefitinib, drug resistance