目的 探討白花蛇舌草醇提取物（EEHD）、半枝蓮醇提取物（EESB）及其聯(lián)用的體內(nèi)外抗胰腺癌作用及機制。方法 MTS法檢測不同濃度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）聯(lián)合對胰腺癌Panc28、胰腺導管上皮Hped6-C7細胞生長的影響，Chou-Talalay法評價兩藥聯(lián)合的作用效果；人胰腺癌裸鼠移植性腫瘤模型評價EEHD、EESB（200 mg/kg）及二者聯(lián)用（100 mg/kg+100 mg/kg、50 mg/kg+150 mg/kg、150 mg/kg+50 mg/kg）的體內(nèi)抗腫瘤作用； ELISA法檢測EEHD（50 μg/mL）、EESB（50 μg/mL）及EEHD+EESB（25 μg/mL+25 μg/mL）對Panc28、ASPC-1細胞上清葡萄糖及乳酸水平的影響；Western Blotting法檢測其對PKM2/PKM1蛋白表達的影響。結果 EEHD、EESB均能有效抑制胰腺癌細胞的增殖，兩藥聯(lián)合指數(shù)（I）值均小于1，提示二者具有協(xié)同作用。體內(nèi)實驗表明，與模型組比較，各給藥組均可顯著抑制胰腺癌生長（P<0.05），聯(lián)用組作用明顯優(yōu)于單藥組，且1：1比例效果最好。與對照組比較，兩藥單用、聯(lián)用均可顯著抑制葡萄糖攝取、乳酸分泌并降低PKM2/PKM1比率，且聯(lián)用效果更好（P<0.05）。結論 EEHD、EESB聯(lián)用體內(nèi)外均可協(xié)同抑制胰腺癌的生長，其機制可能與影響腫瘤糖酵解有關。

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

國家自然基金面上項目（81774191）；北京市自然基金面上項目（1172031）；北京市屬高校高水平教師隊伍建設支持計劃青年拔尖人才培育計劃（CIT&TCD201804086）