3-methyladenine抑制自噬诱导胰腺癌细胞SW1990失巢凋亡

【目的】 探讨3-methyladenine(3-MA)对人胰腺癌SW1990细胞增殖?迁移及失巢凋亡的影响作用及其机制?【方法】 以胰腺癌细胞SW1990及永生化胰腺导管上皮细胞H6C7为研究对象,设3-MA处理组及PBS对照组,采用软琼脂克隆培养法及Poly-HEMA悬浮培养法筛选抵抗失巢凋亡的细胞?Annexin V-FITC/PI双染和TUNEL试剂盒法检测细胞凋亡;免疫荧光法及透射电镜检测细胞自噬;CCK-8法检测细胞增殖; Transwell小室检测细胞迁移能力?【结果】永生化胰腺导管上皮细胞H6C7处理组及对照组均无集落形成,胰腺癌细胞SW1990处理组形成(2.3 ± 2.63)个集落,对照组形成(9 ± 3)个,与H6C7 相比,SW1990具有较强的抵抗失巢凋亡的能力 (P < 0.05)?3-MA可抑制胰腺癌SW1990细胞自噬(P < 0.05)并抑制其增殖及迁移能力(P < 0.01)且诱导失巢凋亡(P < 0.01)?【结论】 3-MA可诱导胰腺癌细胞SW1990失巢凋亡,其机制可能与细胞自噬受抑有关?

3-Methyladenine Impairs Anoikis Resistance of Pancreatic Cancer SW1990 Cells Through Inhibiting Autophagy In Vitro

【Objective】 To investigate the effect and mechanism of 3methyladenine (3MA) on proliferation, migration, and autophagy of human pancreatic cancer cell line SW1990. 【Methods】 The experimental objects were pancreatic cancer cell line SW1990 and human immortalized, nontumorigenic pancreatic ductal epithelial cell line H6C7. We divided them into the control group and 3MA group. Acquisition of anoikis resistance cells was obtained by soft agar clone culture and polyHEMA suspension culture. Cell apoptosis was detected by Annexin VFITC/PI and TUNEL. Autophagy assay was measured by immunofluorescence and electronic microscope. Cell proliferation ability was detected by CCK8. Transwell assay was performed to examine the migration ability. 【Results】 Compared with H6C7 cells (no clones formation), pancreatic cancer SW1990 cells (2.3± 2.63) in treatment group, (9 ± 3) in control group showed anoikis resistance (P < 0.05). 3MA could inhibit autophagy of SW1990 cells under electronic microscope (P < 0.05), which could also inhibit the proliferation and migration ability of SW1990 cells (P < 0.01) and impair anoikis resistance (P < 0.01).【Conclusion】 3MA may induce anoikis of pancreatic cancer cell SW1990 through autophagy inhibition.