Roles of conventional and complementary therapies in recurrent hepatocellular carcinoma

Table 4 Compounds for reversing drug resistance

Compound or Chinese herbal medicine	Conventional drug	Cell line	Molecular mechanism	Ref.
Trametes robiniophila Murr	Oxaliplatin	BEL-7404, SMMC-7721	↓YAP and apoptosis related proteins	Tao et al[104]
Falcarindiol	Cisplatin	Huh7, LM3	↓STAT3/PTTG1 pathway	Hong et al[105]
Dihydroartemisinin	Doxorubicin	Mutant p53 (R248Q)-expressing Hep3B	Modulate p53 (R248Q)-ERK1/2-NF-κB pathway. ↓P-gp expression	Yang et al[106]
Solanum nigrum	Cisplatin and doxorubicin	Hep3B, HepJ5	↑Cleavage of caspase-7. ↑LC-3 A/B II. ↑Apoptosis, autophagy	Wang et al[107]
Bufalin	5-FU	BEL-7402/5-FU	↑Apoptosis arrested the cell cycle at the G0/G1 phase. ↑Bax/Bcl-xL ratio. ↓MRP1, thymidylate synthase (inhibit drug efflux pump activity)	Gu et al[108]
H1 (a derivative of tetrandrine, molecular formula: C27H40N2O6Br)	5-FU	BEL-7402/5-FU	↓STAT3/MCL-1 pathway. ↑PUMA expression	Li et al[109]
Artesunate	Sorafenib	SK-hep1, SMMC-7721	↑Apoptosis. ↓RAF/MAPK pathway. ↓PI3K/AKT/mTOR pathway	Jing et al[110]
Tetrandrine	Sorafenib	SMMC-7721, PLC/PRF/5	↓PI3K/AKT/mTOR pathway. ↓Proliferation. ↑Apoptosis	Niu et al[111]
Bufalin	Sorafenib	HepG2, Huh7	↓p-Akt. Modulate IRE1 pathway	Zhai et al[112]
Solamargine	Sorafenib	HepG2, Huh7	↓lncRNA HOTTIP and TUG1. Modulate HOTTIP-TUG1/miR-4726-5p/mucin 1 pathway	Tang et al[113]
8-bromo-7-methoxychrysin	Sorafenib	SMMC-7721	↓Migration and invasion. ↓N-cadherin. ↑E-cadherin ↑Apoptosis in LCSLCs. ↓HIF-1α and EMT regulator Twist1	Zou et al[114]
Icaritin	Doxorubicin and lenvatinib	Hepa1-6, Huh7	↑Mitophagy and apoptosis. ↑Immunogenic cell death	Yu et al[115]

Akt: Protein kinase B; Bax: BCL2-Associated X Protein; Bcl-xL: B-cell lymphoma extra- large; EMT: Epithelial-mesenchymal transition; ERK: Extracellular signal-regulated kinase; HIF: Hypoxia-Inducible Factor; HOTTIP: HOXA distal transcript antisense RNA; IRE1: Inositol-requiring enzyme 1; LC-3 A/B II: Microtubule-associated protein-1 light chain-3 A/1B II; LCSLC: Liver cancer stem-like cell; MCL-1: Myeloid cell leukemia 1; MRP1: Multidrug Resistance Protein 1; mTOR: Mammalian target of rapamycin; NF-κB: Nuclear factor kappa B; PI3K: Phosphatidylinositol 3-kinase; PTTG1: Pituitary tumor transforming gene 1; RAF: Rapidly accelerated fibrosarcoma; STAT3: Signal transducer and activator of transcription 3; TUG1: Taurine upregulated 1; YAP: Yes-associated protein; 5-FU: 5-fluorouracil.