Background Endometrial carcinoma is one of the most common female tract genital malignant tumors.Nifedipine,an L-type calcium channel antagonist can inhibit cell proliferation of carcinomas.Recent studies indicated that a rise in the free cytosolic calcium ([Ca2+]c) was a potent inducer of autophagy.Here,we investigated the relationship between nifedipine and autophagy in Hec-1A cells.Methods Cells were cultured with nifedipine (10 μmol/L) and harvested at different times for counting cell number.MTT assay was applied to evaluate the cell viability and transwell assay to reveal cell migration.Apoptotic cells were detected with annexin V/PI assay.Then cells were treated with 3-methyladenine (3-MA) (2.5 mmol/L) for 0,5,15,30,60,and 120 minutes and the expression of the L-type calcium channel alpha1D (Cav1.3) protein was detected.At last,cells were cultured and assigned to four groups with different treatment:untreated (control group),10 pmol/L nifedipine (N group),2.5 mmol/L 3-MA (3-MA group),and 10 μmol/L nifedipine plus 2.5 mmol/L 3-MA (N+3MA group).Autophagy was detected with GFP-LC3 modulation by fluorescent microscopy,and expression of the autophagy-associated proteins (LC3,Beclin1 and P70s6K) by Western blotting and monodansylcadaverine (MDC) labeled visualization.Results Proliferation of Hec-1A cells was obviously suppressed by nifedipine compared with that of the untreated cells for 24,48,and 96 hours (P=0.000 for each day).The suppression of migration ability of the nifedipine-treated cells (94.0±8.2) was significantly different from that of the untreated cells (160.00±9.50,P=0.021 ).The level of early period cell apoptosis induced by nifedipine was (2.21±0.19)％,which was (2.90±0.13)％ in control group (P=0.052),whereas the late period apoptosis level reached (10.38±0.96)％ and (4.40±0.60)％ (P=0.020),respectively.The 3-MA group induced a slight increase in the Cav1.3 levels within 15 minutes,but significantly attenuated the Cav1.3 levels after 30 minutes.There were more autophagic vacuoles labeled by MDC in the N group (20.63±3.36) than the control group (6.29±0.16,P=0.015).GFP-LC3 localization revealed that the LC3 levels of cells in 3-MA group,N+3MA group,3-MA group were 2.80±0.29,2.30±0.17,and 1.80±0.21,respectively.Cells in the N group showed significant augmentation of autophagy (P＜0.05).Western blotting analysis confirmed the down-regulation of LC3 levels in 3-MA group (0.85±0.21) and N+3MA group (1.21 ±0.12) compared with nifedipine treatment (2.64±0.15,P ＜0.05).The annexin-V-FITC/PI assay showed that the level of early period cell apoptosis induced in the N+3-MA group ((11.22±0.91)％) differed significantly from that of the control group ((2.51±0.70)％) and N group ((3.47±0.39)％).Similarly,the late period level of the N+3-MA group ((55.19±2.51)％) differed significantly from that of the control group((15.81±1.36)％) and the N group ((22.09±2.48)％,P＜0.05).The down-regulated expression of P70s6k and up-regulated expression of the Beclin1 revealed significant differences between the N+3-MA group and control group (=0.025; Beclin1:P=0.015).Conclusions Proliferation and migration in vitro of endometrial carcinoma Hec-1A cells are significantly suppressed by nifedipine.The nifedipine leads autophagy to oppose Hec-1A cells apoptosis.Autophagy inhibition by 3-MA leads down-regulation of Cav1.3 and enhances nifedipine-induced cell death.The nifedipine-induced autophagy is linked to Beclin1 and mTOR pathways.