S100A6 Induces the Resistance to Gefitinib in Human Lung Adenocarcinoma PC9 Cell Lines with EGFR 19 Exon Mutations.

Abstract

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.