Table 3.
Effect and mechanism of plant-derived natural products in combination with immunotherapy.
| Combination Therapy | Concentration | Cell Line/Model | Mechanism | Reference |
|---|---|---|---|---|
| Lycium barbarum polysaccharide/ CXCL10 |
lycium barbarum polysaccharide: 100 mg/kg CXCL10: 15 µg/kg |
H22 mice model | Improved immune function and promoted secretion of Th1 cytokines and restore balance of Thl/Th2, improved number and function of DC cells and intervened immune suppression state of tumor-bearing bodies | (214) |
| Vitamin C/ Anti-PD-L1 antibody |
vitamin C: 4 g/kg Anti-PD-L1 antibody: 75 µg/3day |
Hepa1-6 cancer mice | Activated cyclic GMP-AMP synthase (cGAS) and promoted the secretion of its product cGAMP, and then activated the STING pathway of vascular endothelial cells | (215) |
| 10-hydroxycamptothecinc/DC hepa1-6fusion vaccine | 10-hydroxycamptothecinc: 50-100 µg/mL | Hepa1-6 cancer mice | Induced improving immune function and inducing significantly CTL cytotoxicity | (216) |
| Chinese herb medicine/ Camrelizumab/ Lenvatinib |
camrelizumab: 200 mg/3weeks lenvatinib: 8 mg/day |
Advanced liver cancer patient | Improved symptoms of abdominal distension and jaundice, nutritional status and quality, alleviated the pain, and prolonged overall survival time | (217) |
| Fuling sini decoction/Sorafenib | sorafenib: 800 mg/day | Liver cancer patient | Improved the survival outcome of patients with advanced primary liver cancer, improve immune function | (218) |
| Paclitaxel/ Anti-CD133 antibody |
nanoparticles: 7.51-56.92 ng/mL |
Huh-7 HepG2 |
Targeted liver cancer stem cells and induced apoptosis | (221) |
| Paclitaxel/ Anti-human stathmin1antibody |
paclitaxel: 0.1-1.6 µg/mL anti-human stathmin l antibody: 10-160 µg/mL |
HepG2 | Inhibited proliferation and induced apoptosis | (222) |
| Taxol/ Cyclosporin A |
taxol: 0.1 µmol/L cyclosporin A: 0-10 µmol/L |
Hep3B HepG2 HA22T VGH Hepa 1-6 |
Increased the expression of caspase-9 and caspase-3, induced apoptosis of liver cancer cells through PI3K-mTOR pathway, and effectively reversed drug resistance of paclitaxel | (223) |
| Gambogic acid/ Bortezomib |
gambogic acid: 0.4-0.6 µmol/L bortezomib: 40-60 nmol/L |
HepG2 H22 |
Induced cytotoxicity and enhanced proteasome inhibition and ER stress | (224) |
| Camptothecin/ Etoposide/ Tunicamycin |
camptothecin:3 μmol/L etoposide: 5 μmol/L tunicamycin: 1 μg/mL |
Hep3B | Induced resistance through up-regulating GRP78 and block G1 phase cell cycle | (225) |
| Nicotinamide/ STAT3 inhibitor |
nicotinamide: 5 mmol/L S3I-201:100 µmol/L stattic: 1.5 µmol/L |
HepG2 | Reduced phosphorylation of STAT3 Y705, down-regulated the expression of SNAIL1, VEGFA and ZEB1, and decreased epithelial-mesenchymal transition and glucose metabolism | (226) |
| Hypocrellin B/ Transferrin/ Membrane |
TF-CCCM-HB-NPs: 0-100 µg/mL | HepG2 LO2 HepG2 tumor-bearing mice model |
Promoted the production of ROS and reduced MMP, inhibited the growth of tumor in mice model with liver cancer, prolonged the survival time of tumor-bearing mice | (227) |
| Doxorubicin/ miRNA-122 |
sCDP/DOX/miR-122: 2.1 µg/mL | Hep G2 Liver nude mice bearing tumor |
Increased the expression of p53 and cleaved caspase-3, downregulated the expression of Bcl-w and CCNG1 leading to irreversible cell apoptosis, decreased the expression of MDR1, MRP and P-gp, and improved the sensitivity to DOX of HepG2 cells | (228) |
| Doxorubicin/ Combretastatin A-4 phosphate disodium |
Fe2O3-PDA-Dox: 0.4 mg/mL CA4P: 0.1 mg/mL |
Liver tumor rats model | Enhanced the combined treatment of transcatheter arterial chemoembolization and photothermal ablation without additional increase in liver and kidney toxicity | (229) |
| Mannose/ Tumor-assoclated antigens |
M/CpG-ODN-H22-Lipo: 100 µL/mice |
H22 bearing mice model | Induced the activation and maturation of DCs in vivo and the activated DCs stimulated effector cells to kill tumor cells in mice | (230) |
| Docetaxel/ Tubacin |
docetaxel: 0-32 µmol/L tubacin: 10 µmol/L |
SNU449 SNU387 |
Arrested the cell cycle, inhibit metastasis and proliferation, as well as induce apoptosis of liver cancer cells | (231) |
| Evodiamine/ Chloroquine |
evodiamine: 10 μmol/L chloroquine: 25 μmol/L |
HepG2 | Inhibited angiogenesis through inducing autophagy, and decreased the expression of VEGFA and inhibited invasion | (232) |
| Evodiamine/ Paclitaxel/ CDK1 inhibitors |
evodiamine:1-4 μmol/L paclitaxel: 0.2 μmol/L R0306: 2 μmol/L |
HepG2 | Decreased the expression of Bcl-2 and cyclin B1, increased the expression of Bax and cyclin E | (233) |
| Compound kushen injection/ Sorafenib |
compound kushen injection: 0.43-1.32 mg/mL sorafenib: 10, 30 mg/kg |
Hepa1-6 tumor nude mice | Activated proinflammatory responses and relieved immunosuppression of tumor-associated macrophages in the liver cancer cell microenvironment by triggering tumor necrosis factor receptor superfamily member 1 (TNFR1)-mediated NF-κB and p38 MAPK signaling cascades | (234) |