MicroRNA (miR)-355 Suppressed Small Cell Lung Cancer Cell Metastasis via Regulating P38 Mitogen-Activated Protein Kinases (MAPKs) Signaling

MicroRNA (miR)-355 was reported to mediate p38 mitogen-activated protein kinases (MAPKs) signaling, which exerted an effect on cell invasion and metastasis. But whether miR-355 could inhibit small cell lung cancer cell line H446 cell metastasis by regulating p38 MAPKs signaling needs further study. H446 cells were cultured to establish miR-355 overexpression group and blank group. The expression of MT1-MMP, the activity and migration of H446 cells were evaluated. Further, the ability of invasion, the level of p-p38 MAPKs and the activity degree of MT1-MMP were observed in H446 cells. MT1-MMP was mainly expressed on the cell membrane. miR-355 overexpression significantly decreased cellular viability and reduced MT1-MMP and p-p38 MAPKs levels relative to the blank group without influencing p38 MAPKs level. In addition, miR-355 overexpression suppressed cell migration and invasive ability in H446 cells. Finally, miR-355 overexpression reduced pro-MMP and MMP-2 activity in H446 cells. miR-355 overexpression suppressed H446 cell metastasis through regulating P38 MAPKs signaling.

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Erianthridin suppresses non-small-cell lung cancer cell metastasis through inhibition of Akt/mTOR/p70S6K signaling pathway

Scientific Reports ◽

10.1038/s41598-021-85675-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sutthaorn Pothongsrisit ◽

Kuntarat Arunrungvichian ◽

Yoshihiro Hayakawa ◽

Boonchoo Sritularak ◽

Supachoke Mangmool ◽

...

Keyword(s):

Lung Cancer ◽

Cell Migration ◽

Protein Kinase ◽

Small Cell Lung Cancer ◽

Cancer Metastasis ◽

Small Cell ◽

Migration And Invasion ◽

Lung Cancer Cell ◽

Small Cell Lung ◽

Cell Metastasis

AbstractCancer metastasis is a major cause of the high mortality rate in lung cancer patients. The cytoskeletal rearrangement and degradation of extracellular matrix are required to facilitate cell migration and invasion and the suppression of these behaviors is an intriguing approach to minimize cancer metastasis. Even though Erianthridin (ETD), a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits various biological activities, the molecular mechanism of ETD for anti-cancer activity is unclear. In this study, we found that noncytotoxic concentrations of ETD (≤ 50 μM) were able to significantly inhibit cell migration and invasion via disruption of actin stress fibers and lamellipodia formation. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 was markedly downregulated in a dose-dependent manner after ETD treatment. Mechanistic studies revealed that protein kinase B (Akt) and its downstream effectors mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K) were strongly attenuated. An in silico study further demonstrated that ETD binds to the protein kinase domain of Akt with both hydrogen bonding and van der Waals interactions. In addition, an in vivo tail vein injection metastasis study demonstrated a significant effect of ETD on the suppression of lung cancer cell metastasis. This study provides preclinical information regarding ETD, which exhibits promising antimetastatic activity against non-small-cell lung cancer through Akt/mTOR/p70S6K-induced actin reorganization and MMPs expression.

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