Solamargine inhibits gastric cancer progression by regulating the expression of lncNEAT1_2 via the MAPK signaling pathway

Int J Oncol. 2019 May;54(5):1545-1554. doi: 10.3892/ijo.2019.4744. Epub 2019 Mar 12.


Solamargine, a derivative from the steroidal solasodine in Solanum species, has exhibited anticancer activities in numerous types of cancer; however, its role in gastric cancer (GC) remains unknown. In the present study, it was demonstrated that Solamargine suppressed the viability of five gastric cancer cell lines in a dose‑dependent manner and induced notable alterations in morphology. Treatment with Solamargine promoted cell apoptosis (P<0.01). Solamargine increased the expression of long noncoding RNA (lnc) p53 induced transcript and lnc nuclear paraspeckle assembly transcript 1 (NEAT1)_2 (P<0.01) in GC by reducing the phosphorylation of extracellular signal‑regulated kinase (Erk)1/2 mitogen‑activated protein kinase (MAPK). To gain insight into the potential mechanism, an Erk1/2 inhibitor (U0126) was applied. The results revealed that lncNEAT1_2 expression levels increased, which was consistent with the effects of Solamargine. Downregulation of lncNEAT1_2 in GC cells revealed no effect on the expression levels of total Erk1/2 and, and counteracted the effect of Solamargine. Solamargine was observed to increase the expression of lncNEAT1_2 via the Erk1/2 MAPK signaling pathway. Of note, the knockdown of lncNEAT1_2 reduced the inhibitory effect of Solamargine (P<0.05). Additionally, experiments in vivo and in primary GC cells from patients demonstrated that Solamargine significantly suppressed tumor growth (P<0.05). In vivo analysis of a xenograft mouse model further supported that Solamargine could induce the apoptosis of cancer cells in tumor tissue as observed by a terminal deoxynucleotidyl transferase‑mediated dUTP‑biotin nick end labeling and H&E staining (P<0.05). Experiments in primary GC cells from patients verified the anti‑tumor effect of Solamargine. In summary, the findings of the present study indicated that Solamargine inhibited the progression of GC by regulating lncNeat1_2 via the MAPK pathway.

MeSH terms

  • Animals
  • Butadienes / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Nitriles / pharmacology
  • RNA, Long Noncoding / genetics*
  • Solanaceous Alkaloids / administration & dosage*
  • Solanaceous Alkaloids / pharmacology
  • Stomach Neoplasms / drug therapy*
  • Up-Regulation
  • Xenograft Model Antitumor Assays


  • Butadienes
  • NEAT1 long non-coding RNA, human
  • Nitriles
  • RNA, Long Noncoding
  • Solanaceous Alkaloids
  • U 0126
  • beta-solamarine