Tissue Distribution and Anti-Lung Cancer Effect of 10-Hydroxycamptothecin Combined with Platycodonis Radix and Glycyrrhizae Radix ET Rhizoma

Abstract

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.

Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo

“…TCM can act on multiple components of interest at once, which is likely key to reversing MDR. 14 − 17 …”

“…In recent years, combining traditional Chinese medicine (TCM) with chemotherapeutic drugs to combat MDR has been proposed. TCM can act on multiple components of interest at once, which is likely key to reversing MDR. − …”

Pharmacokinetic interaction between a Chinese herbal formula Huosu Yangwei oral liquid and apatinib in vitro and in vivo

“…This finding may partially explain why HSYW decrease the incidence rate of the side effects of this anticancer agent, owing to the highest plasma exposure is always tightly linked to the frequency of the side effects of therapeutic drugs, especially for those drugs with a narrow therapeutic window. [ 38 ]…”

Traditional Chinese medicine formula T33 inhibits the proliferation of human colorectal cancer cells by inducing autophagy

“…Four ingredients of T33, specifically Gansui (Kansui Radix), Zhigancao (Glycyrrhizae Radix et Rhizoma Praeparata cum Melle), Baishao (Paeoniae Radix Alba), and Jiangbanxia (Pinelliae Rhizoma Praeparatum Cum Zingibere et Alumine), are known as Gan Sui Ban Xia Tang, which has long been used in the treatment of spontaneous diarrhea and malignant pleural effusion 16,17 . Much evidence has also indicated that each component of T33 has been used in treatments for various cancers 15,18–26 . However, information about the effects of T33 on colon cancer is still limited.…”

“…16 , 17 Much evidence has also indicated that each component of T33 has been used in treatments for various cancers. 15 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 However, information about the effects of T33 on colon cancer is still limited.…”