Adjuvant role of traditional Chinese medicine in postoperative gastric cancer

Table 2 Anti-gastric cancer effects and corresponding mechanisms of traditional Chinese medicine formulae

TCM formulae	Compounds/constituents	Functions	Clinical stage	Experimental model	Effect	Specific mechanisms (pathways/targets)	Ref.
Sijunzi decoction	Radix Glycyrrhiizae (Gancao), Radix Ginseng (Renshen), Poria cocos Schw. (Fuling) and Rhizoma Atractylodes (Baizhu)	Nourishing spleen and enrich qi	GC tumor recurrence and treatment resistance	In vitro (MKN74 cellsand MKN45 cells)	Anti-tumor	Inhibit the nuclear accumulation and DNA-binding of β-catenin	[14]
Fuzheng Huoxue anticancer prescription	Codonopsis pilosula (Franch.) N annf Astragalus membranaceus (Fisch.) Bge, Atractylodes macrocephala Koidz, Poria cocos (Schw.) Wolf, Rehmannia glutinosa (Gaertn.) Lib osch, Adenophoratetraphylla (Thunb.) Fisch, Salvia miltiorrhiza Bge, and Angelica sinensis (Oliv.) Diels	Replenish vital functions (Zhengqi), improve blood stasis and circulation	Mid- or late-stage GC	In vitro (SGC-7901). In vivo (female nude mice)	Correct a hypercoagulatory state, improve immunologic function, extend patient survival times, and inhibit gastric tumor growth	NS	[13]
SRRS	Atractylodes macrocephala koidz (Baizhu), Poria cocos Schw. (Fuling), Sargentodoxa cuneata (Oliv.) Rehd. Et Wils. (Daxueteng), Prunella vulgaris L. (Xiakucao) and etc	Nourishing spleen	Advanced GC	In vitro (SGC-7901). In vivo (female BALB/C-nu/nu mice)	Inhibition of gastric cancer cell growth	Decrease the expression of bcl-2 mRNA inducing apoptosis	[109]
Composed Chinese medicine of Huachansu	Arenobufagin (11.14%), bufalin (18.67%), bufotalin (7.33%), cinobufagin (16.67%), cinobufotalin (16.74%), gamabufotalin (8.45%), resibufogenin (12.03%), and telocinobufagin (8.97%)	Anticancer	Advanced GC	In vitro (SGC7901, MGC803 and NCM460)	Suppression of proteasome activities and increase of ROS levels	Regulating PI3K/AKT and MAPK signaling pathways	[110]
Xiaojianzhong decoction	cassia twigs, paeonia, roasted licorice, ginger, jujube, and maltose sugar	Nourishing spleen and stomach, anticancer	GC	In vitro (AGS, HGC-27, and GES-1)	Suppressing the viability of GC cells, inducing apoptosis, arresting these cells in the G0/G1 phase, and inhibiting cell clone formation	Inhibiting the expression of IL6, PTGS2, MMP9, MMP2, and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein	[111]
Yiqi Huayu decoction	Huangqi, Dangshen, Chenpi, Banxia, Baizhu, Baishao, Danggui, Sanleng, Ezhu, Sheshecao, Shijianchuan, Fulin, Muxiang, Sharen, and Gancao	Invigorating qi and invigorating spleen and removing blood stasis	GC after stage II and III operations	In vitro (AGS)	Anti-recurrence and metastasis of GC	Affecting the JAK2-STAT3 pathway and the expression of ACSL4, and induction of ferroptosis	[35]
Weifuchun	Radix Ginseng Rubra (red ginseng), Rabdosia amethystoides H. Hara (Xiangchacai), and fried Fructus Aurantii (Zhike)	Strengthen the spleen and replenish qi, promote blood circulation and detoxification, and alleviate flatulence and phlegm	GC	In vitro (AGS, MKN45, and SGC7901)	Inhibiting proliferation, migration, and inducing apoptosis in GC cells	Targeting candidate genes (TNFa, IL6, VEGFA, NFKB, MAPK1, and BAX)	[26]
				In vitro (NCI-N87, SNU-5, SNU-16, GES-1 cells, and Hs.738. St/Int cells)	Suppressing the malignant cellular phenotypes of GC cells	miR-26a-5p-mediated KPNA2 destabilization and the disruption of the MAPK pathway also enhances the repression of KPNA2	[32]
Daikenchuto	Zanthoxylum fruit (Huajiao), processed dried ginger (Ganjiang), ginseng (Renshen), and malt sugar (Maiyatang)	Stimulates intestinal motility	POI following abdominal surgery	In vivo (male BALB/c mice)	Recovery of the delayed intestinal transit	Inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1 may be partly mediated by activation of α7nAChR	[40]
Jianpi Yangzheng decoction	Astragali Radix (Huang Qi) (60 g), Codonopsis Radix (Dang Shen) (30 g), Sparganii Rhizoma (San Leng) (15 g), Curcumae Rhizoma (E Zhu) (15 g), Atractylodis Macrocephalae Rhizoma (Bai Zhu) (10 g), Angelicae Sinensis Radix (Dang Gui) (10 g), Paeoniae Alba Radix (Bai Shao) (10 g), Aucklandiae Radix (Mu Xiang) (10 g), Citri Reticulatae Pericarpium (Chen Pi) (10 g), and Glycyrrhizae Radix (Gan Cao) (5 g)	Anticancer, anti-metastasis	GC after chemotherapy	In vitro (MFC murine GC cell). In vivo (615-strain mice)	Impeding pre-metastatic niche formation and exhibiting anti-tumor metastasis effect	Reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment	[30]
				In vitro (MKN28, AGS, HGC-27, MKN74, MKN45 and MFC). In vivo (male BALB/c-nude mice)	Inhibitory effect on GC growth and metastasis	Elevates the abundance of CLDN18.2 in gastric cancer, suppresses the activity of YAP/TAZ signaling	[31]
				In vitro (AGS, HGC -27). In vivo (BALB/c nude mice)	Inhibit the invasion and migration of GC	Regulating TAM-exos miR-513 b-5p mediated PTEN/AKT signaling	[29]
Modified Jian-pi-yang-zheng decoction	-	Qi-invigorating, spleen-strengthening and stasis-removing	Advanced GC	In vitro (HGC-27 and THP-1 monocytes). In vivo (mice (615-strain)	Suppressed GC growth and metastasis	Inhibit GC cell EMT via PI3Kγ-dependent TAM reprogramming	[28]
Modified Gexia-Zhuyu Tang	Peach kernel (9 g), Safflower (9 g), Angelica sinensis (9 g), Chuanxiong (6 g), Red peony (6 g), Peony bark (6 g), YanhuSuo (3 g), Wulingzhi (6 g), Wuyao (6 g), Fructus Aurantii (4.5 g), Xiangfu (4.5 g), Licorice (9 g), Rhizoma atractylodis macrocephalae (12 g), Rhizoma curcumae (9 g), Hedyotis diffusa (15 g), and Scutellaria barbata (15 g)	Anticancer	GC	In vitro (MFC). In vivo (BALB/c male mice)	Inhibited GC tumor progression	Inhibits the growth, proliferation, metastasis, and invasion of GC by regulating the intestinal flora and promotes pyroptosis of GC	[43]
Xiaotan Sanjie recipe	Rhizoma Arisaematis, Pinellia Ternata, Atractylodes Macrocephala, Poria Cocos, Fritillaria sichuanensis, White Mustard Seed, Fructus aurantii, Pericarpium Citri Reticulatae, Radish Seed, Galli Gigerii Endothelium Corneum and Medicated Leaven (5:5:4:4:3:3:3:3:2:2:1)	Anti-metastasis	Advanced GC	In vitro (GC-7901, HGC-27, MKN-28, MKN-45, MGC80-3, BGC-823, MKN-7 and KAO-II). In vivo (Female BALB/c-nude mice)	Prevented GC metastasis	Inhibits the GnT-V-mediated E-cadherin glycosylation and promotes the E-cadherin accumulation at cell-cell junctions	[17]
				In vitro (SGC-7901 cells and HUVEC)	Inhibit angiogenesis in GC	Inhibit angiogenesis in gastric cancer through IL-8-linked regulation of the VEGF pathway	[18]
Banxia Xiexin decoction	Pinellia ternata (Thunb.) Makino 12 g, Zingiber officinale Roscoe 9 g, Scutellaria baicalensis Georgi 9 g, Coptis chinensis Franch. 3 g, Panax ginseng C.A.Mey. 9 g, Ziziphus jujuba Mill 12 g, and Glycyrrhiza uralensis Fisch 9 g	Protecting the gastrointestinal mucosa, improving gastrointestinal diseases, regulating human endocrine metabolism	Advanced GC	In vitro (AGS and GES-1)	Inhibits invasion, metastasis, and epithelial mesenchymal transition in GC	Inhibition of lncRNA TUC338 expression	[37]
Compound kushen injection	Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Heterosmilacis)	Anticancer, improve body immunity, relieve of cancer pain and bleeding	Advanced GC	In vitro (AGS, HGC-27, MKN-45, MKN-74, GES-1). In vivo (male mice)	Inhibit GC growth and metastasis, improve body's immunity, and protect normal tissues from damage	Regulating VCAM1 induced by the TNF signaling pathway to inhibit epithelial-mesenchymal transition of GC	[34]
				In vitro (BGC-803/MKN-28)	Inhibited GC cell growth and migration and induced GC cell apoptosis	Regulating the EMT process in GC cells through the PI3K/AKT signalling pathway	[33]
Yiwei decoction	Astragalus Membranaceus, Pinellia Ternate, Tetrastigma Hemsleyanum Diels et Gilg, Actinidia chinensis Planch, Ophiopogon Japonicus, Taraxacum mongolicum Hand, Paeonia lactiflora Pall, Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf, and Rabdosia amethstoides (Benth.) Hara	Anticancer, supplementing qi and strengthening the body	GC recurrence and metastasis	In vitro (HGC-27 , MFC, S180 cells). In vivo (Wistar rats)	Inhibit the proliferation of tumor cells	Inhibition of GC cell proliferation by spleen-derived exosomes inducing apoptosis	[11]
Ziyin Huatan recipe	Lilii Bulbus (Baihe.), Pinelliae Rhizoma (Fabanxia) and Hedyotis Diffusa (Baihuasheshecao)	Anti-metastasis	Advanced GC	In vitro (MGC-803 and SGC-790). In vivo (male BALB/c nude mice)	Inhibit migration and invasion of GC	Relate to the upregulation of RUNX3 expression	[19]
				In vitro (HGC27 and MGC803). In vivo (male BALB/c nude mice)	Inhibit cell proliferation and promote apoptosis in GC	Decrease the expression of Bcl-2 and Cyclin D1, modulate PI3K/AKT signaling pathway by inhibiting PI3K expression	[20]
Qi Ling decoction	Astragalus, Smilacisglabrae, Atractylodesmacrocephalae, Scutellariabarbata, Salvia chinensis, Benth, Eupolyphagasteleophaga, Agrimonia, and Forsythia suspense	Anti-metastasis, anti-tumor	Advanced GC	In vitro (BGC-823 and SGC-7901)	Inhibit the invasion, migration, and adhesion of GC cells	Inhibition of MMP-9 expression through the PI3K/AKT signaling pathway	[24]
Babao Dan	Natural bezoar, snake gall, antelope horn, pearl, musk, and Panax notoginseng	Anti-metastasis, anti-tumor	Advanced GC	In vitro (AGS and MGC80-3)	Inhibits the migration and invasion of GC cells	Inhibit TGF-β-induced EMT and inactivating TGF-β/Smad signaling in GC cells	[36]

TCM: Traditional Chinese medicine; GC: Gastric cancer; NS: Not stated CAG: Chronic atrophic gastritis; MAPK: Mitogen-activated protein kinase; KPNA2: Karyopherin subunit Alpha 2; POI: Postoperative ileus; SCFA; Short-chain fatty acids; VACM1: Vascular cell adhesion molecule 1; TNF: Tumor necrosis factor; MMP: Matrix metalloproteinases; TAM: Tumor-associated macrophages; HUVEC: Human umbilical vein endothelial cells; VEGF: Vascular endothelial growth factor; SGC: Stem cell growth factor; ROS: Reactive oxygen species; PI3K: Phosphoinositide 3-kinase; AKT: Protein kinase B; IL6: Interleukin 6; PTGS2: Prostaglandin-endoperoxide synthase 2; CCL2: C-C motif chemokine ligand 2; JAK2: Janus kinase 2; STAT3: Signal transducer and activator of transcription 3; ACSL4: Acyl-CoA synthetase long-chain family member 4; VEGFA: Vascular endothelial growth factor A; NF-κB: Nuclear factor kappa B; BAX: BCL2-associated X protein; MCP-1: Monocyte chemoattractant protein-1; YAP: Yes-associated protein; TAZ: Transcriptional coactivator with PDZ-binding motif; PTEN: Phosphatase and tensin homolog; EMT: Epithelial-mesenchymal transition; PI3Kγ: Phosphoinositide 3-kinase gamma; TAM: Tumor-associated macrophages; GnT-V: N-acetylglucosaminyltransferase V; VEGF: Vascular endothelial growth factor; RUNX3: Runt-related transcription factor 3; TGF-β: Transforming growth factor beta; Smad: Sma and mad related protein.