Zuo Jin Wan, a Traditional Chinese Herbal Formula, Reverses P-gp-Mediated MDRIn VitroandIn Vivo

Abstract

Zuo Jin Wan (ZJW), a typical traditional Chinese medicine (TCM) formula, has been identified to have anticancer activity in recent studies. In this study, we determined the underlying mechanism of ZJW in the reversal effect of multidrug resistance on colorectal cancer in vitro and in vivo. Our results showed that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs in HCT116/L-OHP, SGC7901/DDP, and Bel/Fu MDR cells. Moreover, combination of chemotherapy with ZJW could reverse the drug resistance of HCT116/L-OHP cells, increase the sensitivity of HCT116/L-OHP cells to L-OHP, DDP, 5-Fu, and MMC in vitro, and inhibit the tumor growth in the colorectal MDR cancer xenograft model. ICP-MS results showed that ZJW could increase the concentration of chemotherapeutic drugs in HCT116/L-OHP cells in a dose-dependent manner. Furthermore, we showed that ZJW could reverse drug resistance of colorectal cancer cells by decreasing P-gp level in vitro and in vivo, which has been represented as one of the major mechanisms that contribute to the MDR phenotype. Our study has provided the first direct evidence that ZJW plays an important role in reversing multidrug resistance of human colorectal cancer and may be considered as a useful target for cancer therapy.

miR200c Attenuates P-gp–Mediated MDR and Metastasis by Targeting JNK2/c-Jun Signaling Pathway in Colorectal Cancer

“…Flow cytometry was used to detect apoptosis by determining the relative amount of Annexin V-FITC-positivepropidium iodide -negative cells, as previously described (26). Unstained cells, cells stained with Annexin V-FITC alone, and cells stained with propidium iodide alone were used as controls.…”

“…Immunofluorescence analyses of P-gp in MDR cells were done as previously described (26). Briefly, cells were incubated with the following primary antibodies: P-gp, JNK2, p-JNK, and p-c-Jun, washed by PBS, and incubated with desmin antibody (1:400), followed by incubation with fluorescence-conjugated antibody.…”

Hedyotis diffusa Willd overcomes 5-fluorouracil resistance in human colorectal cancer HCT-8/5-FU cells by downregulating the expression of P-glycoprotein and ATP-binding casette subfamily G member 2

“…In addition, traditional Chinese prescriptions and formulae, which are based on TCM principles, have been demonstrated to be effective in the treatment of breast carcinoma (12), gastric cancer (13) and CRC (14). The reported benefits of applying TCM as an anticancer therapy have included effectively controlling cancer progression, improving the quality of life and prolonging patient survival (15)(16)(17)(18)(19)(20)(21)(22).…”

The effect of multidrug resistance modulator HZ08 on pharmacodynamics and pharmacokinetics of adriamycin in xenograft-nude mice

“…However, it produced disappointing results in vivo because, its low binding affinities necessitated the use of high doses, which therefore resulted in unacceptable adverse effects (Krishna and Mayer, 2000). Furthermore, many new compounds have been reported with notable effect of reversing MDR through some specific targets (Zhao et al, 2012;Liu et al, 2013;Sui et al, 2013). However, few of them have undergone the test of toxicity which can probably enhance the side effects of chemotherapeutic agents.…”