Although bromocriptine (BRC) as first-line drug is recommended for treating patients with prolactinoma, a minority of patients with prolactinoma are resistance to BRC. Moreover, our previous study showed the difference in drug sensitivity in BRC-treated rat prolactinoma cells, MMQ cells are more resistant to BRC, and GH3 cells are more sensitive to BRC. Curcumin (Cur) has been shown to inhibit proliferation of prolactinoma cell lines. The aim of this study is to further investigate whether Cur could enhance the growth-inhibitory effect of BRC resistance on prolactinoma cell lines and its possible mechanism. CCK-8 kit was used to test cell growth. Cell cycle analysis and apoptosis were performed by flow cytometry. Electron microscopy was used to test autophagosome. The mRNA expression profiles were analyzed using the Affymetrix Gene-Chip array. Western blot was used to test protein expression. Our data showed that Cur enhanced the growth-inhibitory effect of BRC on GH3 and MMQ cell proliferation. BRC and Cur both induced cell apoptosis, and Cur could significantly increase the apoptosis of BRC on pituitary adenoma cells through the ERK/EGR1 signaling pathway. Moreover, Cur could enhance the autophagic cell death (ACD) of BRC on tumor cells by inhibiting the AKT/GSK-3β signaling pathway. The same results were confirmed invivo study. Taken together, Cur sensitizes rat prolactinoma cells to BRC by activating the ERK/EGR1 and inhibiting the AKT/GSK-3β signaling pathway.

尽管溴隐亭（BRC）作为一线药物被推荐用于治疗泌乳素瘤患者，但少数泌乳素瘤患者对BRC耐药。此外，我们之前的研究表明，BRC 处理的大鼠泌乳素瘤细胞的药物敏感性存在差异，MMQ 细胞对 BRC 的耐药性更强，而 GH3 细胞对 BRC 的敏感性更高。姜黄素 (Cur) 已被证明可抑制泌乳素瘤细胞系的增殖。本研究的目的是进一步研究Cur是否可以增强BRC抗性对催乳素瘤细胞系的生长抑制作用及其可能的机制。CCK-8 试剂盒用于测试细胞生长。通过流式细胞术进行细胞周期分析和细胞凋亡。电子显微镜用于测试自噬体。使用 Affymetrix 基因芯片阵列分析 mRNA 表达谱。Western印迹用于测试蛋白质表达。我们的数据显示，Cur 增强了 BRC 对 GH3 和 MMQ 细胞增殖的生长抑制作用。BRC和Cur均能诱导细胞凋亡，Cur可通过ERK/EGR1信号通路显着增加BRC对垂体腺瘤细胞的凋亡。此外，Cur 可通过抑制 AKT/GSK-3β 信号通路增强 BRC 对肿瘤细胞的自噬性细胞死亡 (ACD)。体内研究证实了相同的结果。总之，Cur 通过激活 ERK/EGR1 和抑制 AKT/GSK-3β 信号通路使大鼠泌乳素瘤细胞对 BRC 敏感。Cur 可通过 ERK/EGR1 信号通路显着增加 BRC 对垂体腺瘤细胞的凋亡。此外，Cur 可通过抑制 AKT/GSK-3β 信号通路增强 BRC 对肿瘤细胞的自噬性细胞死亡 (ACD)。体内研究证实了相同的结果。总之，Cur 通过激活 ERK/EGR1 和抑制 AKT/GSK-3β 信号通路使大鼠泌乳素瘤细胞对 BRC 敏感。Cur 可通过 ERK/EGR1 信号通路显着增加 BRC 对垂体腺瘤细胞的凋亡。此外，Cur 可通过抑制 AKT/GSK-3β 信号通路增强 BRC 对肿瘤细胞的自噬性细胞死亡 (ACD)。体内研究证实了相同的结果。总之，Cur 通过激活 ERK/EGR1 和抑制 AKT/GSK-3β 信号通路使大鼠泌乳素瘤细胞对 BRC 敏感。