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. 2023 Feb 14;13:1116532. doi: 10.3389/fonc.2023.1116532

Figure 2.

Figure 2

Mechanisms of natural products and combination therapy against liver cancer. Alkaloids could inhibits migration through up-regulating TGF-β/Smad and miR-199a-5p, and down-regulating HIF-α expression. Terpeniods promotes apoptosis by inhibiting the PI3K/AKT pathway and the expression of caspase3. It also induces autophagy through up-regulating the expression of LC3II and Beclin-1. Ployphenols inhibits Cyclin D1 and CDK1/4 expression, which in turn block the cell cycle. It also induces apoptosis by activating ATF6/CHOP signaling pathway. Flavonoids induces apoptosis through activation of the ATF6/CHOP pathway and upregulation the ratio of Bax/Bcl-2. Moreover, other natural products inhibit migration through down-regulating VEGFR2-AKT-ERK1/2 signaling pathway and suppressing EMT. Combination of Natural product ingredients inhibits Cyclin D1 and CDK1/4 expression through downregulation of the Wnt/β-catenin pathway, which in turn inhibits cell proliferation. It also reverses multidrug resistant by decreasing the expression of P-gP, MRP and BCRP. Natural product in combination with chemotherapy suppress angiogensis through down-regulating VEGF and Ang expression. It also induces autophagy by upregulating expression of LC3ii and Beclin-1. Natural product in combination with immunotherapy act by inducing antitumor effects through restoring immune recognition and immune elimination by regulating the immune function. It also induces apoptosis by inhibiting the PI3K/AKT and p38MAPK pathway, which in turn induces apoptosis.