@Article{biocell.2021.012504,
AUTHOR = {DAN ZHANG, HAIJING LIU, ZHENNAN YI, YUANYUAN LU, YANYAN CHEN, WEIQIANG SU, HUIBING LIN, ZHIHUI ZHANG, WEI LEI},
TITLE = {Thymidylate synthase confers pemetrexed resistance of non-small cell lung cancer cells by EGFR/PI3K/AKT pathway},
JOURNAL = {BIOCELL},
VOLUME = {45},
YEAR = {2021},
NUMBER = {3},
PAGES = {617--625},
URL = {http://www.techscience.com/biocell/v45n3/41689},
ISSN = {1667-5746},
ABSTRACT = {Chemotherapy drug resistance is the main cause leading to the relapse and metastasis of non-small cell lung
cancer (NSCLC) patients. Our study aimed to investigate the mechanism of pemetrexed resistance in NSCLC. Firstly,
the pemetrexed (PEM)-resistant PC-9 and A549 lung adenocarcinoma cell lines (PC-9/PEM and A549/PEM) were
established. The expression of thymidylate synthase (TS) in PC-9/PEM, A549/PEM, A549, and PC-9 cells were
analyzed by qRT-PCR and western blot. Then, cell viability, colony formation, migration, and invasion were
performed on PEM-resistant cells transfected with TS siRNA. The role of EGFR in PEM resistance of PEM-resistant
cells was investigated using EGFR siRNA. The effects of gefitinib and EGFR siRNA on EGFR/PI3K/AKT pathway and
downstream signaling Cyclin D1 and E2F1 in PEM-resistant cells were analyzed. Results showed that the protein level
of TS was significantly increased in A549/PEM and PC-9/PEM. TS knockdown inhibited the potency of proliferation,
colony-forming potential, migration, and invasion in PEM-resistant cells. EGFR knockdown abrogated the resistance
to PEM of PEM-resistant cells and suppressed the migration and invasion of PEM-resistant cells. Gefitinib treatment
and EGFR knockdown respectively inhibited the EGFR/PI3K/AKT pathway and downregulated Cyclin D1 and E2F1
in PEM-resistant cells. Thus, TS might be a predictive marker for PEM resistance in NSCLC. Inhibition of the EGFR
pathway abrogated the resistance to PEM and inhibited the EGFR/PI3K/AKT and downstream signaling of PEMresistant NSCLC cell lines.},
DOI = {10.32604/biocell.2021.012504}
}