PDF(Pubmed)
Abstract：
Background: Solute carrier family 3 member 2 (SLC3A2) is highly expressed in various types of cancers, including bladder cancer (BLCA). However, the role and mechanism of SLC3A2 in the onset and progression of BLCA are still unclear. Methods: The interfering plasmid for SLC3A2 was constructed and transfected into BLCA cells. Cell proliferation, invasion, and migration abilities were assessed to evaluate the impact of SLC3A2 silencing on BLCA cell growth. M1 and M2 macrophage polarization markers were detected to evaluate macrophage polarization. The levels of reactive oxygen species (ROS), lipid peroxidation, and Fe2+, as well as the expression of ferroptosis-related proteins, were measured to assess the occurrence of ferroptosis. Ferroptosis inhibitors were used to verify the mechanism. Results: The experimental results showed that SLC3A2 was highly expressed in BLCA cell lines. The proliferation, invasion, and migration of BLCA cells were reduced after interfering with SLC3A2. Interference with SLC3A2 led to increase the expression of M1 macrophage markers and decreased the expression of M2 macrophage markers in M0 macrophages co-cultured with tumor cells. Additionally, interference with SLC3A2 led to increased levels of ROS, lipid peroxidation, and Fe2+, downregulated the expression of solute carrier family 7 member11 (SLC7A11) and glutathione peroxidase 4 (GPX4), while upregulated the expression of acyl-coA synthetase long chain family member 4 (ACSL4) and transferrin receptor 1 (TFR1) in BLCA cells. However, the impact of SLC3A2 interference on cell proliferation and macrophage polarization was impeded by ferroptosis inhibitors. Conclusion: Interference with SLC3A2 inhibited the growth of BLCA cells and the polarization of tumor-associated macrophages by promoting ferroptosis in BLCA cells.
摘要：
背景：溶质载体家族3成员2（SLC3A2）在各种类型的癌症中高表达，包括膀胱癌（BLCA）。然而,SLC3A2在BLCA发病和进展中的作用和机制尚不清楚。方法:构建SLC3A2干扰质粒,转染BLCA细胞。细胞增殖，入侵,评估SLC3A2沉默对BLCA细胞生长的影响。检测M1和M2巨噬细胞极化标志物以评价巨噬细胞极化。活性氧（ROS）的水平，脂质过氧化，和Fe2+，以及铁凋亡相关蛋白的表达，进行测量以评估铁死亡的发生。使用铁凋亡抑制剂来验证该机制。结果:SLC3A2在BLCA细胞系中高表达。扩散,入侵,干扰SLC3A2后，BLCA细胞的迁移减少。干扰SLC3A2导致与肿瘤细胞共培养的M0巨噬细胞中M1巨噬细胞标志物的表达增加，M2巨噬细胞标志物的表达降低。此外,对SLC3A2的干扰导致ROS水平增加，脂质过氧化，和Fe2+，下调溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX4）的表达，同时上调BLCA细胞中酰基辅酶A合成酶长链家族成员4（ACSL4）和转铁蛋白受体1（TFR1）的表达。然而,铁凋亡抑制剂阻碍了SLC3A2干扰对细胞增殖和巨噬细胞极化的影响。结论:干扰SLC3A2可促进BLCA细胞的铁凋亡,从而抑制BLCA细胞的生长和肿瘤相关巨噬细胞的极化。
