Ganoderma lucidum extract reverses hepatocellular carcinoma multidrug resistance via inhibiting the function of P-glycoprotein in vitro and in vivo

Cancer is a leading cause of death globally. Chemotherapy still plays an indispensable role in the clinical treatment of cancer. However, the emergence of multidrug resistance (MDR) has greatly obstructed the further application of chemotherapy agents. Ganoderma lucidum (G. lucidum) is a traditional Chinese medicine as well as an edible mushroom. In this study, we first explored the effect of six extract samples derived from G. lucidum on the cell viability of adriamycin-resistant human hepatocellular carcinoma multidrug-resistant cell subline (HepG-2/ADM). All these samples showed no obvious toxicity to cells; however, only G. lucidum ethanol extract could reverse resistance to doxorubicin and paclitaxel. Then the P-glycoprotein (P-gp) function in hepatocellular carcinoma G2 (HepG-2) and HepG-2/ADM cells was determined after incubated with these samples, and we found that G. lucidum ethanol extract could inhibit P-gp function in vitro. Furthermore, G. lucidum ethanol extract could reverse resistance to paclitaxel in HepG-2/ADM tumor-bearing mice in vivo, while the protein expression level of P-gp was unchanged. Taken together, these results indicated the potential role of G. lucidum ethanol extract in reversing MDR in the clinical treatment of hepatocellular carcinoma.