Fe3+抑制醋酸棉酚对脑胶质瘤细胞的杀伤作用

目的：探讨人脑胶质瘤微环境中Fe³⁺对醋酸棉酚(gossypol acetate, GAA)杀伤脑胶质瘤细胞的影响。方法：用不同浓度GAA(0、5、10、15、20、25 μmol/L)处理人脑胶质瘤LN229、SW1783、U87MG、U251MG细胞，CCK-8法检测细胞活性，计算GAA半数致死量(IC₅₀)。将4种脑胶质瘤细胞各分为4组：对照组、Fe³⁺组、GAA组、Fe^{3+ ₊}GAA组，分别予以培养基，FeCl ₃·6H₂O，GAA，FeCl₃·6H₂O+ GAA处理。GAA浓度以各胶质瘤细胞IC₅₀为准，FeCl₃·6H₂O浓度与GAA浓度相同。CCK-8法检测细胞活性；Transwell实验检测细胞迁移情况；运用流式细胞术分析脑胶质瘤细胞凋亡水平。结果：GAA显著抑制胶质瘤细胞活性，对LN229、SW1783、U87MG、U251MG细胞IC₅₀分别为9.38、9.56、14.53、10.39 μmol/L。与对照组相比，Fe³⁺组细胞增殖变化不明显，GAA组细胞增殖和迁移显著抑制(P<0.05)；与GAA组相比，Fe³⁺ +GAA组细胞活性和迁移能力明显增强(P<0.05)，细胞凋亡水平显著降低(P<0.05)。结论：Fe ³⁺抑制GAA对人脑胶质瘤细胞的杀伤作用。

Fe3+inhibits the killing effect of gossypol acetate on glioma cells

Objective: To investigate the effect of iron ion (Fe ³⁺ ) in human glioma microenvironment on gossypol acetate (GAA) killing glioma cells. Methods: Human glioma cells LN229, SW1783, U87MG and U251MG were treated with different concentrations of GAA (0, 5, 10, 15, 20, 25 μmol/L). CCK-8 assay was used to detect the cell viability and calculate the half inhibitory concentration (IC₅₀). The 4 types of glioma cells were divided into 4 treatment groups: control group, Fe³⁺ group, GAA group, Fe³⁺+GAA group, treated with medium, FeCl₃·6H₂O, GAA, FeCl₃·6H₂O+GAA separately. The concentration of GAA was selected based on the IC₅₀ of each glioma cell, and the concentration of FeCl₃·6H₂O was the same as that of GAA. CCK-8 assay was used to detect the cell proliferation ability. Transwell assay was used to detect cell migration ability, and the flow cytometry was used to analyze the rate of apoptosis in the glioma cells. Results: GAA significantly inhibited the proliferation of glioma cells, and the IC₅₀ of GAA to LN229, SW1873, U87MG, U251MG was 9.38, 9.56, 14.53, 10.39 μmol/L. Compared with the control group, the proliferation of glioma cells was not significantly changed in the Fe³⁺ group, while the proliferation and migration of cells were significantly inhibited in the GAA group(P<0.05). Compared with GAA group, the activity and migration of tumor cells were significantly enhanced in the Fe³⁺+GAA group(P<0.05), and the level of apoptosis was decreased obviously(P<0.05). Conclusion: Fe ³⁺ could inhibit the killing effect of GAA on human glioma cells.［Key words］glioma; iron metabolism; gossypol acetate; apoptosis; transferrin receptor c