Table 2.
Combination Therapy of Rg3 in HCC
| Drug or TACE | Model | Types | Dosage | Activity and Mechanisms | References |
|---|---|---|---|---|---|
| Doxorubicin | In vitro In vivo |
SK-Hep1 HepG2 Huh-7 Hep3B Athymic BALB/c nude mice |
Doxorubicin (2.5μM) Rg3 (100 μM) Doxorubicin (1mg/kg) Rg3 (20 mg/kg) |
Sensitized doxorubicin-induced cancer cell death and Inhibited autophagy possibly by blocking lysosomal function via regulating gene expression such as CHOP | [88] |
| Recombinant human TRAIL | In vitro In vivo |
SK-Hep1 HepG2 Hep3B Huh-7 Male nude mice |
TRAIL (25 ng/mL) Rg3 (100 mmol/L) TRAIL (3 mg/kg) Rg3 (20 mg/kg) |
Sensitized TRAIL-induced cancer cell death CHOP-mediated DR5 upregulation | [87] |
| Sorafenib | In vitro In vivo |
HepG2 Huh7 Five-week-old BALB/c nude mice |
Sorafenib (2.5–20μM) combined with Rg3 (50μg/ml and 100μg /ml) Sorafenib (30 mg/kg) Rg3 (5 mg/kg) |
Sensitized sorafenib-induced cancer cell death by modulating PTEN/AKT signaling pathway | [84] |
| Sorafenib | In vitro | HepG2 Bel7404 |
Sorafenib (5μM) Rg3 (130 μM) |
Relieved the hepatocellular tumor progression through regulating the HK2-mediated glycolysis and PI3K/AKT signaling pathway | [85] |
| Artesunate | In vitro In vivo |
HepG2-SR Male 7-week-old BALB/c-nu/nu mice |
Artesunate (10, 15 mM) Rg3(50, 75 mM) Rg3 (6mg/kg) Artesunate (7.5 mg/kg) Rg3 (12 mg/kg) Artesunate (15 mg/kg) |
Overcoming sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling | [86] |
| Oxaliplatin | In vitro | SMMC-7721 | Oxaliplatin (0.25 μg/ml) Rg3 (15μg/ml) |
Inhibited the proliferation and promoted apoptosis of hepatocellular carcinoma cells via downregulating PCNA and cyclin D1 | [74] |
| Cyclophosphamide | In vivo | Tumor-bearing C57BL/6 mice | Cyclophosphamide (20.0 mg/kg) Rg3 (3.0 mg/kg) |
Increased survival time | [69] |
| TACE | In vitro In vivo |
HepG2 Adult male New Zealand white rabbits |
25-100 mg/l Rg3 (6.0 mg/kg) |
Induced VX2 liver tumor cell apoptosis and inhibited angiogenesis | [91] |
| TACE | In vivo | Male and female Buffalo rats | Rg3 (1 mg/kg) | Effectively limited HCC tumor progression, reduced metastasis, and increased overall survival. | [92] |
| TACE | Clinical Trial | 228 patients with advanced HCC | Rg3 at 20 mg twice a day was administered for 2 months as one course | Prolonged overall survival | [93] |