The research of As4S4 inhibit the growth of breast cancer cell by regulating phosphatidylinositol 3 kinase/protein kinase B/mammalian target of rapamycin signal pathway

Abstract

Objective To investigate the effect of As4S4 inhibit the growth of breast cancer cell by regulating phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signal pathway. Methods Methyl thiazol tetrazolium (MTT) assay was used to detect breast cancer cell MCF-7 proliferation after 0, 20, 40, 60, 80 μmol/L As4S4 treatment for 24, 48, 72 h, and 10 μmol/L LY294002 treatment 48 h. Wound healing and transwell were used to detect the distance of MCF-7 cell migration and invasion after As4S4 dealing with 48 h. Flow cytometry was used to detect MCF-7 cell apoptosis after and 10 μmol/L LY294002 treatment 48 h. Western blotting was used to detect PI3K, p-Akt, mTOR expression levels in MCF-7 cell after As4S4 and 10 μmol/L LY294002 dealing with 48 h. Results Compared with 0 μmol/L treatment, 20 μmol/L As4S4 had no significant inhibition of cell proliferation at 24 h (P=0.065), it had a significant inhibition of cell proliferation at 48 h and 72 h (P=0.033) with the inhibition ratio of 11.1% and14.3%, respectively.40, 60, 80 μmol/L As4S4 treatment had the most obvious inhibitory effect at 72 h (P=0.002) the inhibition ratio of 47.9%, 58.8%, 67.1%, respectively. After60 As4S4 treatment for 48 h, the migration rate and invasion ability of MCF-7 cell were lower than the control group (with decrease of 42.4%), the difference was significant (P=0.005), the apptosis rate was significant increased to (19.56±1.12)% (P=0.009), the expression of PI3K in MCF-7 cell had no significantly change and p-Akt, mTOR were significantly decreased than control group (P=0.008) with the decrease of 64.3% and 58.7%, respectively. The results of proliferation and apoptosis was consistent with the LY294002 treatment. Conclusion As4S4 may inhibit breast cancer MCF-7 cell proliferation and metastasis and promote apoptosis by inhibiting PI3K/Akt/mTOR signaling pathway. Key words: As4S4; Breast cancer; Proliferation; Transfer; Apoptosis