Tissue Distribution and Anti-Lung Cancer Effect of 10-Hydroxycamptothecin Combined with Platycodonis Radix and Glycyrrhizae Radix ET Rhizoma
Tissue Distribution and Anti-Lung Cancer Effect of 10-Hydroxycamptothecin Combined with Platycodonis Radix and Glycyrrhizae Radix ET Rhizoma
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10-羟基喜树碱联合桔梗、甘草ET的组织分布及抗肺癌作用
DOI：
10.3390/molecules24112068
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发表时间：
2019-05
期刊：
影响因子：
4.6
通讯作者：
Haifang Chen
中科院分区：
文献类型：
--
作者：
Wugang Zhang;Mulan Li;Wendi Du;Wuliang Yang;Guofeng Li;Chen Zhang;Xinli Liang;Haifang Chen
10-羟基喜树碱（Hydroxycamptothecin，HCPT）是一种广谱化疗药物，但其毒副作用和多药耐药（multidrug resistance，MDR）限制了其临床应用。一系列的药物传递系统已被用来克服其缺点，并保持其治疗效果，但使用的传统中药（中药）的运输效应，以改善化疗药物的分布还没有广泛的报道。桔梗和甘草是临床常用的中药，常作为药对配伍，起“转运剂”的作用。本研究采用超高效液相色谱-串联质谱（UHPLC-MS/MS）技术，研究了JG和GC（JGGC）对羟基喜树碱（HCPT）组织分布的影响及其联合治疗后的抗肿瘤疗效。此外，还观察了其对多药耐药蛋白（P-gp和LRP）表达的影响，以及对荷刘易斯肺癌C57 BL/6 J小鼠的免疫调节和协同抗凋亡作用。结果表明，JGGC显著增加HCPT的药时曲线下面积（AUC）和平均滞留时间（MRT），降低清除率（CL）。联合用药可降低HCPT诱导的LRP、P-gp和Bcl-2/Bax水平。JGGC还显著升高RBC、PLT、HGB、IL-2和IFN-γ水平，降低IL-10水平。总之，当HCPT与JGGC联合使用时，通过抑制外排蛋白，观察到组织中HCPT的浓度增加，通过促进细胞凋亡和由于Th 1/Th 2偏移的逆转引起的免疫，观察到抗癌作用的协同增强。本研究结果为JGGC与化疗药物联合应用于临床的可行性提供了参考。
10-Hydroxycamptothecin (HCPT) is a broad-spectrum chemotherapeutic drug, although its side effects and multidrug resistance (MDR) limit its clinical application. A range of drug delivery systems have been utilized to overcome its shortcomings and maintain its therapeutic efficacy, however the use of the transport effect of traditional Chinese medicines (TCMs) to improve the distribution of chemotherapeutic drugs has not been widely reported. Platycodonis Radix (JG) and Glycyrrhizae Radix ET Rhizoma (GC) are common TCMs in clinics and are often combined as drug pairs to act as “transport agents”. In the present study, the effect of JG and GC (JGGC) on the distribution of HCPT in tissues and its antitumor efficacy after being combined as a therapy were investigated, for which ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used. Furthermore, the effect on the protein expression of multidrug resistance proteins (P-gp and LRP), and the immunomodulatory and synergistic antiapoptotic effect on Lewis lung cancer-bearing C57BL/6J mice were also evaluated. The results demonstrate that JGGC significantly increased the area under the concentration time curve (AUC) and mean residence time (MRT) and reduced the clearance rate (CL) of HCPT. In addition, the combined use of JGGC decreased the levels of LRP, P-gp and Bcl-2/Bax when treated with HCPT. JGGC also significantly elevated the levels of RBCs, PLTs, HGB, IL-2, and IFN-γ, and decreased IL-10 levels. In summary, an increased concentration of HCPT in tissues was observed when it was combined with JGGC through inhibition of efflux protein, with a synergistic enhancement of the anticancer effect observed through promotion of apoptosis and immunity due to a reversion of the Th1/Th2 shift. Our findings provide a reference for the feasibility of combining JGGC with chemotherapy drugs in clinical applications.
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DOI：
--
发表时间：
2015
期刊：
Chinese Journal of Experimental Traditional Medical Formulae
影响因子：
--
作者：
Huang We
通讯作者：
Huang We
影响因子：
9.7
作者：
De Vera AA;Gupta P;Lei Z;Liao D;Narayanan S;Teng Q;Reznik SE;Chen ZS
通讯作者：
Chen ZS
DOI：
10.1016/s0021-9258(17)38654-4
发表时间：
1985-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Yaw-Huei Hsiangl;Robert Hertzbergj;Sidney Hechtj;Leroy F. LiuS
通讯作者：
Yaw-Huei Hsiangl;Robert Hertzbergj;Sidney Hechtj;Leroy F. LiuS
影响因子：
20.4
作者：
Mateu-Jimenez, Merce;Curull, Victor;Barreiro, Esther
通讯作者：
Barreiro, Esther
DOI：
--
发表时间：
2005
期刊：
Journal of Shandong Univenity
影响因子：
--
作者：
Xu Hon
通讯作者：
Xu Hon