目的 探讨白花蛇舌草醇提取物（EEHD）、半枝莲醇提取物（EESB）及其联用的体内外抗胰腺癌作用及机制。方法 MTS法检测不同浓度EEHD、EESB（200.0、100.0、50.0、25.0、12.5、0 μg/mL）及不同比例（1：3、1：1、3：1）联合对胰腺癌Panc28、胰腺导管上皮Hped6-C7细胞生长的影响，Chou-Talalay法评价两药联合的作用效果；人胰腺癌裸鼠移植性肿瘤模型评价EEHD、EESB（200 mg/kg）及二者联用（100 mg/kg+100 mg/kg、50 mg/kg+150 mg/kg、150 mg/kg+50 mg/kg）的体内抗肿瘤作用； ELISA法检测EEHD（50 μg/mL）、EESB（50 μg/mL）及EEHD+EESB（25 μg/mL+25 μg/mL）对Panc28、ASPC-1细胞上清葡萄糖及乳酸水平的影响；Western Blotting法检测其对PKM2/PKM1蛋白表达的影响。结果 EEHD、EESB均能有效抑制胰腺癌细胞的增殖，两药联合指数（I）值均小于1，提示二者具有协同作用。体内实验表明，与模型组比较，各给药组均可显著抑制胰腺癌生长（P<0.05），联用组作用明显优于单药组，且1：1比例效果最好。与对照组比较，两药单用、联用均可显著抑制葡萄糖摄取、乳酸分泌并降低PKM2/PKM1比率，且联用效果更好（P<0.05）。结论 EEHD、EESB联用体内外均可协同抑制胰腺癌的生长，其机制可能与影响肿瘤糖酵解有关。

Objective This study investigated the inhibitory effects of combined ethanol extract from Hedyotic diffusa (EEHD) and ethanol extract from Scutellaria barbata (EESB) on human pancreatic cancer growth both in vitro and in vivo. Methods The effects of different concentrations (200.0, 100.0, 50.0, 25.0, 12.5 and 0 μg/mL) of Hedyotic diffusa extract, Scutellariae Barbatae extract, and their combinations on pancreatic cancer cell proliferation were detected using MTS assay, and the drug combination were evaluated by Chou-Talalay method. Panc28 pancreatic cells bearing nude mice model was used for evaluating the in vivo antitumor effects of EEHD, EESB(200 mg/kg) and their combinations (100 mg/kg+100 mg/kg, 50 mg/kg+150 mg/kg and 150 mg/kg+50 mg/kg). The effects of EEHD (50 μg/mL), EESB (50 μg/mL) and EEHD + EESB (25 μg/mL + 25 μg/mL) on the levels of glucose and lactate in the supernatant of panc28 and AsPC-1 cells were detected by ELISA, and the effects on the expression of pkm2/pkm1 by Western blotting. Results MTS result showed that combination of both drugs showed more obvious inhibitory effects on pancreatic cancer cells, with the combination index (I)<1, indicating synergistic effects. In vivo result showed that drug combinations showed more obvious inhibitory effects compared to each individual (P<0.05). Also, drug combinations significantly decreased glucose consumption, lactic acid production, and PKM2/PKM1 ratios(P<0.05). Conclusion Combination of EEHD and EESB synergistically inhibited pancreatic cancer cell growth, which might be related with tumor glycolysis.

R285.5

国家自然基金面上项目（81774191）；北京市自然基金面上项目（1172031）；北京市属高校高水平教师队伍建设支持计划青年拔尖人才培育计划（CIT&TCD201804086）