丙泊酚联合卡铂对乳腺癌细胞凋亡及JAK/STAT通路的影响

Effect of Propofol combined with Carboplatin on apoptosis and JAK/STAT pathway

摘要:

目的 探究丙泊酚联合卡铂对乳腺癌细胞增殖、凋亡的影响及其与酪氨酸激酶JAK/转录因子STAT（JAK/STAT）信号通路的关系，以期为疾病的临床治疗提供新思路。方法 在含有100?μmol丙泊酚、20?μmol/L 卡铂、100?μmol丙泊酚+20?μmol/L卡铂培养基中分别培养MCF-7细胞，CCK-8法检测细胞抑制情况；Hoechst33342染色法观察各组细胞形态变化；平板细胞克隆实验检测菌落形成情况；PI/Annexin V-FITC双染法检测细胞凋亡情况；Western blotting检测p-JAK2、p-STAT3、Bcl-2、Bax、Cleaved Caspase-3蛋白表达情况。结果 与对照组比较，丙泊酚组、卡铂组细胞抑制率升高，菌落数量均降低，细胞凋亡率升高（P?<0.05）；与丙泊酚组、卡铂组比较，联合组细胞抑制率升高，菌落数量均降低，细胞凋亡率升高（P?<0.05）。与正常乳腺上皮细胞MCF-10A比较，MCF-7细胞p-JAK2、p-STAT3蛋白表达均升高（P?<0.05）。与对照组比较，丙泊酚组、卡铂组Cleaved Caspase-3、Bax蛋白表达均升高（P?<0.05），p-JAK2、p-STAT3、Bcl-2蛋白表达均降低（P?<0.05）。与丙泊酚组、卡铂组比较，联合组Cleaved Caspase-3、Bax蛋白表达均升高，p-JAK2、p-STAT3、Bcl-2蛋白表达均降低（P?<0.05）。结论 丙泊酚联合卡铂可抑制乳腺癌细胞增殖，诱导其凋亡，其机制可能与抑制JAK/STAT活性，上调凋亡蛋白表达有关。

Abstract:

Objective To explore the influences of Propofol and/or Carboplatin (CBP) on the proliferation and apoptosis of breast cancer cells and its relationship with the tyrosine kinase JAK/transcription factor STAT (JAK/STAT) signaling pathway. Methods MCF-7 cancerous cell line were cultured in Propofol (100?μmol) and/or CBP (20?μmol/L). Cellular inhibitory effect was detected by CCK-8. Morphological changes were observed by Hoechst33342 staining; the colony formation was detected by the clone formation experiment of flat cell; PI/Annexin V-FITC double staining was used to measure apoptosis; the expressions of p-JAK2, p-STAT3, B lymphocyto-2 protein (Bcl-2), Bcl-2 related X protein (Bax) and Cleaved Caspase-3 protein were identified by WB. Results Compared with control group, cell inhibition rate and cell apoptosis rate increased while colony number decreased in Propofol and CBP group in a synergistic manner (P?