2021 Targeted Therapies of Lung Cancer (TTLC) Meeting - Posters-P09. Mechanism of Growth-Inhibitory Effect of Pemetrexed Disodium Heptahydrate on Human PC9 (EGFR Exon 19 Deletion) Cells

P09. Mechanism of Growth-Inhibitory Effect of Pemetrexed Disodium Heptahydrate on Human PC9 (EGFR Exon 19 Deletion) Cells - PDF

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The study investigated the growth-inhibitory effect of pemetrexed disodium heptahydrate on human PC9 cells with EGFR exon 19 deletion. Pemetrexed is commonly used in combination with another drug for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). However, the specific participants and mechanisms of action are not well understood. The researchers aimed to examine the in vitro effects of pemetrexed and further understand its molecular mechanism.<br /><br />The results showed that pemetrexed reduced the proliferation of PC9 cells and induced morphological signs of apoptosis. This apoptotic effect was associated with the generation of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential. Cell cycle analysis revealed that pemetrexed arrested PC9 cells in the G1 phase. Cellular senescence was also observed, which was linked to hyperphosphorylation of pRb and overexpression of CDK.<br /><br />Regarding the molecular mechanism of apoptosis, pemetrexed was found to induce phosphorylation of p53 at ser 15 and ser 46. The expression of extrinsic pathway proteins involved in apoptosis, such as Fas/FasL, DR4/TRAIL, and FADD, was also elevated following pemetrexed treatment.<br /><br />In conclusion, pemetrexed not only induces apoptosis but can also cause specific adverse reactions. The findings suggest that pemetrexed may provide a new target for reducing lung toxicity. The study provides insights into the potential mechanisms underlying the growth-inhibitory effect of pemetrexed on PC9 cells with EGFR exon 19 deletion, contributing to a better understanding of the drug's therapeutic potential in NSCLC treatment.

Asset Subtitle

Md Mohiddin

Meta Tag

Speaker Md Mohiddin

Topic Targeted Therapies - EGFR

Keywords

pemetrexed disodium heptahydrate

PC9 cells

EGFR exon 19 deletion

NSCLC

apoptosis

reactive oxygen species

cell cycle arrest

pRb hyperphosphorylation

p53 phosphorylation

lung toxicity