Department of Pathology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
Department of Pathology, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Drug Dev Res. 2020 Aug;81(5):544-550. doi: 10.1002/ddr.21650. Epub 2020 Feb 25.
To study the relationship between TRIM14 expression and chemotherapy resistance of gastric cancer (GC) cells.
The expression of TRIM14 in 5-fluorouracil (5-FU)- and oxaliplation (L-OHP)-resistant GC tissues and cells were determined by qRT-PCR and western blotting. PcDNA3.1-TRIM14 and shRNA-TRIM14 vector were transfected to 5-FU-resistant GC cells (SGC7901/5-FU), and the proliferation and apoptosis of cells were measured. Animal experiments on 5-FU-resistant GC mice were performed to study the effect of TRIM14 expression on tumor size and weight, GC cell migration, and proliferation. pcDNA3.1-MK-3903 plasmid was transfected to SGC7901/5-FU cells with TRIM14 silence. The cell proliferation and apoptosis were determined. The protein expressions of Trim14, LC3, and BECLIN1 were measured by western blotting.
TRIM14 was significantly upregulated in 5-FU- and L-OHP-resistant GC tissues and cells. The overexpression of TRIM14 promoted the proliferation and autophagy of SGC7901/5-FU cells, and inhibited the apoptosis. Moreover, in vivo experiment verified that the silence of TRIM14 reduced the tumor size and weight, and inhibited the migration and proliferation of GC cells in 5-FU-resistant GC mice. The overexpression of MK-3903 reversed the inhibiting role of TRIM14 knockout on the proliferation and autophagy of SGC7901/5-FU cells.
TRIM14 promoted chemotherapy resistance of GC cells by regulating AMPK/mTOR pathway, and may be a new biomarker for treating GC.
研究 TRIM14 表达与胃癌（GC）细胞化疗耐药性的关系。
采用 qRT-PCR 和 Western blot 检测 5-氟尿嘧啶（5-FU）和奥沙利铂（L-OHP）耐药 GC 组织和细胞中 TRIM14 的表达。将 PcDNA3.1-TRIM14 和 shRNA-TRIM14 载体转染至 5-FU 耐药 GC 细胞（SGC7901/5-FU），检测细胞增殖和凋亡。在 5-FU 耐药 GC 小鼠中进行动物实验，研究 TRIM14 表达对肿瘤大小和重量、GC 细胞迁移和增殖的影响。将 pcDNA3.1-MK-3903 质粒转染至沉默 TRIM14 的 SGC7901/5-FU 细胞，检测细胞增殖和凋亡。采用 Western blot 检测 Trim14、LC3 和 BECLIN1 的蛋白表达。
TRIM14 在 5-FU 和 L-OHP 耐药 GC 组织和细胞中显著上调。TRIM14 的过表达促进了 SGC7901/5-FU 细胞的增殖和自噬，抑制了细胞凋亡。此外，体内实验验证了沉默 TRIM14 可降低 5-FU 耐药 GC 小鼠的肿瘤大小和重量，并抑制 GC 细胞的迁移和增殖。MK-3903 的过表达逆转了 TRIM14 敲除对 SGC7901/5-FU 细胞增殖和自噬的抑制作用。
TRIM14 通过调节 AMPK/mTOR 通路促进 GC 细胞的化疗耐药性，可能成为治疗 GC 的新生物标志物。
