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重楼和莪术提取物与 10-羟基喜树碱联合治疗通过增加血浆浓度增强 H22 肿瘤模型的抗肿瘤作用。

Combination treatment with Rhizoma Paridis and Rhizoma Curcuma longa extracts and 10-hydroxycamptothecin enhances the antitumor effect in H22 tumor model by increasing the plasma concentration.

机构信息

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China; China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.

出版信息

Biomed Pharmacother. 2016 Oct;83:627-634. doi: 10.1016/j.biopha.2016.07.026. Epub 2016 Jul 25.

Abstract

The combination of Western medicine and Chinese prescription is the most effective tumor therapy in China market. In our previous report, a new prescription composed by Rhizoma Paridis and Rhizoma Curcuma longa called LouHuang preparation (LH) shows good antitumor activity. 10-Hydroxycamptothecin (HCPT) as a chemotherapy agent is used for treatment of solid tumors in clinical. In this study, we investigated the combination effect of LH and HCPT on H22 tumor cells in vitro and in vivo. In vitro test, combination of LH and HCPT presented a synergistic effect on H22 cancer cells. Because of the toxicity of HCPT in normal dosage with intraperitoneal injection, we chose a low dose in the study. LH increased the tumor inhibition rate of HCPT in H22 tumor model from 39% to 55% and showed additive effect by the q value method. The concentration of HCPT in plasma was detected by HPLC-FLD method and increased from 60 to 75ng/mL when combined with LH. For the absorption research, LH significantly enhanced the absorption transport of HCPT from 7019.04 to 11569.02ng/cm, while improved the permeation flux (F) and apparent permeability (P) of HCPT from 10.62 to 21.47 (ng/cmmin) and 9.92-20.07 (10cm/s), respectively. The study indicates that LH could boost the efficacy of HCPT by increasing the plasma concentration regardless of the formulation and combined administration of HCPT and LH might be used as an adjuvant drug for treatment of liver cancer.

摘要

西药和中药处方的结合是中国市场上最有效的肿瘤治疗方法。在我们之前的报告中,一种由重楼和莪术组成的新处方称为六黄制剂(LH),显示出良好的抗肿瘤活性。10-羟基喜树碱(HCPT)作为化疗药物,用于临床治疗实体瘤。在这项研究中,我们研究了 LH 和 HCPT 对体外和体内 H22 肿瘤细胞的联合作用。体外试验表明,LH 和 HCPT 联合对 H22 癌细胞具有协同作用。由于 HCPT 在腹腔注射的常规剂量下具有毒性,因此我们在研究中选择了低剂量。LH 使 HCPT 在 H22 肿瘤模型中的肿瘤抑制率从 39%增加到 55%,并通过 q 值法显示出相加作用。通过 HPLC-FLD 法检测血浆中 HCPT 的浓度,当与 LH 联合使用时,浓度从 60 增加到 75ng/mL。对于吸收研究,LH 显著增强了 HCPT 的吸收转运,从 7019.04 增加到 11569.02ng/cm,同时提高了 HCPT 的渗透通量(F)和表观渗透系数(P),分别从 10.62 增加到 21.47(ng/cmmin)和 9.92-20.07(10cm/s)。研究表明,LH 可以通过增加血浆浓度来提高 HCPT 的疗效,而不考虑 HCPT 的配方和联合给药,LH 可能被用作治疗肝癌的辅助药物。

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