目的：研究PERK-ATF4通路的激活水平，以探讨布雷菲德菌素A（BFA）与顺铂（CDDP）的协同抗肺癌的分子机制。方法：以BFA、CDDP单独或联合处理人肺癌GLC-82细胞24、48 h，然后用定量PCR和Western Blot检测PERK、ATF4、p-PERK的表达水平。结果：药物处理24和48 h 后，GLC-82细胞PERK的mRNA和蛋白表达水平在CDDP组最低，在BFA组升高（P＜0．05），在BFA＋CDDP组进一步升高（P ＜0．01），其磷酸化水平均显著降低（P ＜0．01）；ATF4表达在CDDP组中差异无显著性，在BFA组中升高，在BFA＋CDDP组进一步升高（P ＜0．05或P ＜0．01），也高于BFA组和CDDP组（P ＜0．05或P ＜0．01）。结论：BFA联合CDDP上调PERK、ATF4水平，该通路可能是BFA与顺铂协同抗肺癌的分子机制之一。%Objective To investigate the molecular mechanisms of synergistic effects of BFA and CDDP on human lung cancer GLC-82 cells, and to test the levels of PERK-ATF4 pathway. Methods GLC-82 cells were incubated with 50 ng/mL of BFA or/and 2 μg/mL of CDDP for 24 or 48 hours. The levels of PERK, p-PERK and ATF4 in GLC-82 were analyzed by real-time PCRand/or Western Blot. Results The levels of PERK were lowest in CDDP group, but higher in BFA group (P < 0.05), the highest in group of BFA+CDDP (P < 0.05 or P < 0.01). The p-PERK level decreased in group of BFA+CDDP (P < 0.05 or P < 0.01). There was no significant change of ATF4 expression in CDDP group, but ATF4 expression increased slightly in BFA group, and increased further in group of BFA+CDDP (P < 0.05 or P < 0.01)which was also higher than that in BFA group or CDDP group (P < 0.05 or P < 0.01). Conclusions The upregulated levels of PERK and ATF4 by the combination of BFA and CDDP may be one of the mechanisms of synergistic anti-cancer effect of BFA and CDDP on GLC-82 cells.
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