Gastric cancer cell proliferation is inhibited by α-santonin via targeting of PI3K and AKT activation

Lin Nie,Lijiu Zhang

doi:10.4314/tjpr.v19i4.13

Abstract

Purpose: To investigate the effect of α-santonin on proliferation of gastric cancer cells.Methods: Cell proliferation was analysed by 3-4-5-Dimethylthiazol-2-yl-25-diphenyltetrazolium bromide (MTT) assay and migration by wound healing assay. Matrigel coated Transwell chamber was used for determination of cell invasion. Expression of proteins and mRNA was assessed using western blot and RT-PCR assay, respectively.Results: In NUGC4 and MKN45 cell cultures, treatment with α-santonin promoted miR 145 expression significantly when compared to control. Treatment of NUGC4 cells with α-santonin for 48 h significantly increased apoptosis in comparison to control. At 100, 150 and 200 μM concentrations of α-santonin, the level of cell apoptosis increased to 45, 53 and 64 %, respectively (p < 0.05). Treatment with α-santonin caused NUGC4 cell population increase in G1/G0 phase with reduction in S and G2/M phases. A significant reduction in NUGC4 cell invasion was observed following treatment with α-santonin. The α- santonin treatment of NUGC4 cells at 200 μM concentration markedly reduced cell invasion (p < 0.05). Treatment of NUGC4 cells with α-santonin reduced the expression of c Myc, PI3K, and p AKT. The production of MMP-2 and MMP-9 in NUGC4 cells was also decreased by α-santonin treatment.Conclusion: The study demonstrates that α-santonin plays important role in inhibition of gastric cancer cell proliferation by arrest of cell cycle and apoptosis induction. Moreover, the activation of PI3K and AKT was also suppressed by α-santonin. Therefore, α-santonin can potentially be used for the treatment of gastric cancer. Keywords: Apoptosis, MicroRNA, Tumor suppressor, Metastasis, Infiltration

Highlights

Gastric cancer, the second most common cause of deaths associated with cancer, ranks fourth among different types of cancers detected worldwide [1]
The study has demonstrated that α-santonin exhibits inhibitory effect on gastric cancer cell proliferation by arrest of cell cycle and apoptosis induction
The cells plated in 96-well plates at 1 x 106 cells per well density were treated for 48 h with 20, 40, 60, 80, 100, 150 and 200 μM concentrations of α-santonin in DMEM

Summary

INTRODUCTION

The second most common cause of deaths associated with cancer, ranks fourth among different types of cancers detected worldwide [1]. The discovery of molecules which can inhibit metastasis and infiltration of gastric cancer cells as well as suppress their proliferation can form an effective treatment strategy. Studies have shown that miRNAs act as key factors in gastric carcinoma development and progression [8]. It is reported that miR-145 plays inhibitory role in gastric cancer by inhibiting proliferation and tumor metastasis through suppression of MYO6 [10]. Studies investigating mechanism of gastric cancer inhibition by miR-145 have found down-regulation of Sp1 and N-cadherin protein translation [11]. In the present study effect of α-santonin on proliferation and metastasis of gastric cancer cells was investigated and the mechanism involved was studied. The study has demonstrated that α-santonin exhibits inhibitory effect on gastric cancer cell proliferation by arrest of cell cycle and apoptosis induction. The conditions used for culture in the incubator were 37 ̊C in a 5 % CO2 humid atmosphere

Evaluation of cell proliferation

RESULTS

DISCUSSION

CONCLUSION

Conflict of interest