**4.6. Chinese medicines and their active compounds for reversing drug resistance in liver cancer treatment**

Astragaloside is a saponin isolated from Radix Astragali, one of the popular TCM herbs. Astragaloside has been reported to be an effective agent in reversing multidrug resistance (MDR) of cancer treatment. A recent study found that astragaloside can modulate the ex‐ pression of P‐glycoprotein in human hepatic cancer cells Bel‐7402 and reverse 5‐fluoroura‐ cil resistance in chemotherapy. As P‐glycoprotein majorly is responsible for the drug efflux in cancer treatment, the down‐regulation of P‐glycoprotein will inhibit P‐glycopro‐ tein‐mediated drug efflux and improve the efficacy of chemotherapies [47]. Thus, astraga‐ loside may be a potential anticancer drug for reversing drug resistance in liver cancer treatment.

Polyphyllin D is a saponin derived from a TCM herb Paris Polyphylla. The herb of Paris Polyphylla has been used for liver cancer treatment in China for thousands years. Previous study showed that polyphyllin D can induce apoptosis in multi‐drug resistant HepG2 cells [48]. Further mechanism study demonstrated that polyphyllin D may elicit mitochondrial fragmentation in HCC cells. When treating polyphyllin D directly to the isolated mito‐ chondria, the mitochondria exhibited strong swelling with deep transmembrane depolari‐ zation. In addition, significant apoptosis‐inducing factor release could be observed from the multidrug‐resistant HepG2 cells. These results suggest that polyphyllin D may be a potential anti‐cancer agent targeting drug resistance in HCC cells by inducing mitochon‐ drial damage.

Piper betel leaves (PBL) are enriched with medication properties in TCM for many centu‐ ries. Modern researches have proven that PBL has antioxidation activity and may inhibit gene mutation. Recent study has found that PBL extract can inhibit total Glutathione S‐ transferase (GST) and alpha class of GST (GSTA) in HepG2 cells [49]. Further study showed PBL could enhance the sensitivity of HCC cells to chemotherapy. The results revealed that the cytotoxicity of cisplatin was apparently increased in cell with PBL treatment, with the mechanism related to the inhibition of multidrug resistance protein 2. These results indicat‐ ed that PBL extract may reduce drug resistance and improve the efficacy of chemotherapy in liver cancer treatment.
