MT1 Overexpression Affects the Apoptosis and Proliferation of SKOV3 Cells via PI3K/AKT/mTOR Signaling Pathway
XIONG Shu, ZHANG Jun*
Ovarian cancer is a common malignant tumor that severely threatens the health of women. However, the mechanisms of ovarian cancer development remain unclear. This study aimed to investigate the role of the melatonin receptor MT1 in human ovarian cancer SKOV3 cells and explored its primary mechanisms. SKOV3 cells were transfected with the MT1-pcDNA3.1 plasmid (MT1 group) or empty vector pcDNA3.1 (control group), while the untransfected SKOV3 cells were used as the negative control group. After 48 h of transfection, the cells were cultured with fresh medium for 24 h or 48 h, then cell cycle, proliferation and apoptosis were investigated and melatonin expression was measured in the supernatant. Besides, the cells were cultured in serum-depleted medium overnight 48 h after transfection, then replaced with fresh medium containing the PF-04691502 inhibitor (4 μmol/L) and incubated for 24 hours. The protein level of AKT, as well as the total and phosphorylated mTOR protein levels were measured. The results indicated that compared with the NC group, the MT1 group was arrested in the S phase (P<0.05) of cell cycle, concomitant with reduced proliferation and early apoptosis (P<0.05). The secretion of melatonin increased with time in all three groups as detected in the supernatant of cells (P<0.05). Western blot analysis showed that MT1 overexpression inhibited the activation of the PI3K/AKT/mTOR signaling pathway. In conclusion, SKOV3 cells secrete melatonin without any stimulation. The overexpression of MT1 can inhibit PI3K/AKT/ mTOR pathway via binding endogenous melatonin, thereby playing an anticancer role.
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