Abstract
Background: Trillium tschonoskii Maxim (TTM) exerts antitumor effects on a variety of tumour cells. However, the antitumor mechanism of Diosgenin glucoside (DG) extracted from TTM is not clear.
Objective: This study aimed to investigate the anti-tumour effects of DG-induced osteosarcoma MG-63 cells and their molecular mechanism.
Methods: CCK-8 assay, HE staining, and flow cytometry were used to detect the effects of DG on the proliferation, apoptosis, and cell cycle of osteosarcoma cells. Wound healing and Transwell invasion assays were used to observe the effect of DG on the migration and invasion of osteosarcoma cells. The anti-tumour mechanism of DG on osteosarcoma cells was investigated by immunohistochemistry, Western blot, and RT-PCR.
Results: DG significantly inhibited osteosarcoma cell activity and proliferation, promoted apoptosis and blocked the G2 phase of the cell cycle. Both wound healing and Transwell invasion assays showed that DG inhibited osteosarcoma cell migration and invasion. Immunohistochemical and western blot results showed that DG inhibited the activation of PI3K/AKT/mTOR. We found that DG also significantly downregulated the expression of S6K1 and eIF4F, which might be associated with the inhibition of protein synthesis.
Conclusion: DG may inhibit proliferation, migration, invasion, and cell cycle G2 phase arrest of osteosarcoma MG-63 cells and promote apoptosis through the PI3K/AKT/mTOR signalling pathway.
Graphical Abstract
[http://dx.doi.org/10.1586/14737140.2014.863453] [PMID: 24308680]
[http://dx.doi.org/10.3390/ijms21196985] [PMID: 32977425]
[http://dx.doi.org/10.1016/j.canlet.2016.11.019] [PMID: 27894960]
[http://dx.doi.org/10.2165/00148581-200810050-00005] [PMID: 18754698]
[http://dx.doi.org/10.1038/s41571-021-00519-8] [PMID: 34131316]
[http://dx.doi.org/10.1016/j.jep.2019.112304] [PMID: 31626908]
[http://dx.doi.org/10.1002/kjm2.12145] [PMID: 31688993]
[http://dx.doi.org/10.2174/1871520620666200615134039] [PMID: 32538736]
[http://dx.doi.org/10.1016/j.ejphar.2020.172942] [PMID: 31972180]
[http://dx.doi.org/10.1080/15384101.2021.1991121] [PMID: 34658297]
[http://dx.doi.org/10.1007/s12032-020-01369-7] [PMID: 32270306]
[http://dx.doi.org/10.3390/ijms19082274] [PMID: 30072674]
[PMID: 30662624]
[http://dx.doi.org/10.2147/CMAR.S238173] [PMID: 32368141]
[http://dx.doi.org/10.1016/j.bbcan.2020.188405] [PMID: 32827577]
[http://dx.doi.org/10.1101/gad.1212704] [PMID: 15314020]
[http://dx.doi.org/10.1158/2159-8290.CD-15-0460] [PMID: 26293922]
[http://dx.doi.org/10.1186/s12935-021-02397-7] [PMID: 34923996]
[http://dx.doi.org/10.1016/j.phrs.2019.104396] [PMID: 31404628]
[http://dx.doi.org/10.1016/j.molmed.2005.06.007] [PMID: 16002336]
[PMID: 25450580]
[http://dx.doi.org/10.18632/oncotarget.27539] [PMID: 32391118]
[http://dx.doi.org/10.3390/cancers12102972] [PMID: 33066449]
[http://dx.doi.org/10.1101/cshperspect.a033092] [PMID: 29735639]
[http://dx.doi.org/10.1126/scisignal.2005832] [PMID: 25351249]
[http://dx.doi.org/10.1016/j.molcel.2015.01.017] [PMID: 25702871]
[http://dx.doi.org/10.1200/JCO.2011.35.6329] [PMID: 22067397]