2021 Targeted Therapies of Lung Cancer (TTLC) Meeting - Posters-P10. Inhibitory Effect of Pemetrexed Disodium Heptahydrate on the Growth of KRAS-Dependent A549 Lung Cancer Cells

P10. Inhibitory Effect of Pemetrexed Disodium Heptahydrate on the Growth of KRAS-Dependent A549 Lung Cancer Cells - PDF

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This study examined the inhibitory effect of pemetrexed disodium heptahydrate, a drug currently used for the treatment of advanced non-small cell lung cancer, on KRAS-dependent A549 lung cancer cells. The researchers treated A549 cells with pemetrexed for 72 hours and evaluated the results using flow cytometry and western blotting. They observed that pemetrexed induced apoptosis in the cells, as evidenced by increased levels of cleaved caspase-9, cleaved caspase-3, and cleaved PARP. Pemetrexed also caused DNA damage through the production of reactive oxygen species (ROS), increased the expression of pro-apoptotic protein Bax, and induced loss of mitochondrial membrane potential. The drug also induced cellular senescence, as indicated by elevated expression of β-galactosidase. Interestingly, pemetrexed did not inhibit the RAS/RAF/MEK/ERK signaling pathway but induced autophagy via the AMPK/mTOR signaling pathway. The researchers concluded that pemetrexed has potential as a targeted therapy for KRAS-dependent lung cancer due to its ability to induce apoptosis, autophagy, and cellular senescence. These findings provide promising directions for the development of therapies targeting KRAS mutations in lung cancer.

Asset Subtitle

Md Mohiddin

Meta Tag

Speaker Md Mohiddin

Topic Targeted Therapies - KRAS

Keywords

pemetrexed disodium heptahydrate

non-small cell lung cancer

KRAS-dependent A549 lung cancer cells

apoptosis

cleaved caspase-9

DNA damage

reactive oxygen species (ROS)

mitochondrial membrane potential

cellular senescence

autophagy