白屈菜红碱对人结直肠癌细胞凋亡的影响及其机制研究

目的：研究白屈菜红碱（Chelerythrine, CHE）对体外结直肠癌细胞的生长抑制作用,并探讨其作用机制。方法：MTT测定结肠癌细胞存活率,应用流式细胞仪检测CHE处理后ROS的积累和细胞凋亡情况,JC-1(5,5'',6,6''-四氯-1,1'',3,3''-四乙基苯并咪唑羰花青碘化物)荧光染料法检测细胞线粒体膜电位改变,应用荧光显微镜和Western blot法验证ROS积累诱导的线粒体功能障碍。结果：CHE对HCT-116和RKO细胞发挥剂量依赖性细胞毒作用,该作用与ROS介导的凋亡蛋白的表达有关。此外,CHE能够降低伴随线粒体功能障碍的线粒体膜电位。结论：CHE通过ROS介导的线粒体功能障碍和JNKs途径抑制CRC细胞生长并诱导细胞凋亡,提示CHE可能成为潜在的治疗CRC的候选药物。     

Chelerythrine hydrochloride inhibits proliferation and induces mitochondrial apoptosis in cervical cancer cells via PI3K/BAD signaling pathway

Cervical cancer is the fourth most common female cancer worldwide, and drug targeted therapy plays a crucial role in delaying the progression of cervical carcinoma. Chelerythrine hydrochloride (CHE) is a natural alkaloid, which is a focal point in anti-tumor research. In this study, we investigated the effect of CHE on HeLa cells by using MTT assay, RTCA, and colony formation assay. In addition, the flow cytometric analysis, immunofluorescence staining assay and western blot analysis were performed to study the mechanism of CHE. The results showed that CHE exhibited a significant inhibitory effect in HeLa cells, and it could suppress the expression of PI3K subunits in a dose-dependent manner. Moreover, we found that the treatment of CHE further restrained the downstream AKT/mTOR and PKCα signaling. In addition, CHE induced mitochondrial apoptosis of HeLa cells by regulating the BCL-2 family member's expression. Immunofluorescence staining assay indicated that AIF and Cytochrome C were translocated from mitochondria to cytoplasm or nucleus, and notable changes in mitochondrial morphology of HeLa cells were also observed. Finally, the aberrant expression of CHE led to the mitochondrial apoptosis by upregulating the expression of APAF1, Cleaved-Caspase9, Cleaved-Caspase3, and Cleaved-PARP. In summary, CHE suppresses the proliferation of HeLa cells by trigging the mitochondrial apoptosis through the PI3K/BAD signaling pathway.     

Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 Cell

The objective of this study was to evaluate the antitumor activity of chelerythrine chloride (CHE) and investigate its potential apoptotic induction mechanism in SMMC-7721 cells. Our results suggested that the proliferation of SMMC-7721 cells was inhibited by CHE in a time and dose dependent manner, with a significant accumulation in S phase, and the cells exhibited typical apoptotic features. Moreover, CHE remarkably induced apoptosis by disruption of the mitochondrial membrane potential, release of Cyt-c, activation of caspase-3, and cleavage of poly-ADP-ribose polymerase in a dose dependent manner. Furthermore, the expression of Bcl-xl was downregulated while Bax and Bid expression was upregulated, and no variation was found for Bcl-2. These results indicated that CHE may play an important role in suppression of tumor growth by inducing apoptosis in human hepatoma cells via the activation of a mitochondrial pathway and regulating the expression of Bcl-2 family proteins.     

雷公藤红素通过PI3K/AKT/mTOR信号通路对胃癌MFC细胞增殖和凋亡的影响

目的研究雷公藤红素对胃癌MFC细胞内PI3K/AKT/mTOR信号通路的影响及其对胃癌MFC细胞增殖的抑制和促凋亡作用机制。方法分别设置对照组和雷公藤红素低、中、高剂量(5、10、20 mmol/L)组,采用MTT法检测雷公藤红素对胃癌MFC细胞增殖的影响;采用流式细胞技术检测雷公藤红素对胃癌MFC细胞周期的影响及MFC细胞凋亡的情况;Western blotting检测雷公藤红素对胃癌MFC细胞内凋亡相关蛋白Bax、Bcl-2和PI3K、AKT和mTOR蛋白表达的影响;实时定量PCR检测雷公藤红素对胃癌MFC细胞内PI3K、AKT和mTORm RNA表达的影响。结果与对照组比较,雷公藤红素能够呈剂量相关性地显著抑制胃癌MFC细胞的增殖(P0.05);与对照组比较,雷公藤红素能够呈剂量相关性地显著引起MFC细胞G2/M期阻滞(P0.05);与对照组比较,雷公藤红素能够呈剂量相关性地显著促进MFC细胞的凋亡(P0.05);与对照组比较,雷公藤红素能够呈剂量相关性地显著抑制MFC细胞内抗凋亡蛋白Bcl-2蛋白和PI3K、AKT、mTOR蛋白的表达(P0.05),显著促进MFC细胞内促凋亡蛋白Bax的表达(P0.05);与对照组比较,雷公藤红素能够呈剂量相关性地显著抑制MFC细胞内PI3K、AKT和mTORm RNA的表达(P0.05)。结论雷公藤红素能够抑制胃癌MFC细胞的增殖并促进胃癌MFC细胞凋亡,其作用机制可能是通过抑制胃癌MFC细胞内PI3K/AKT/mTOR信号通路中PI3K、AKT、mTOR等蛋白的表达而抑制胃癌MFC细胞的增殖,进而促进胃癌MFC细胞内促凋亡蛋白Bax的表达,同时抑制抗凋亡蛋白Bcl-2的表达,从而促进胃癌MFC细胞凋亡。     

Autophagy plays a protective role against apoptosis induced by toxicarioside N via the Akt/mTOR pathway in human gastric cancer SGC-7901 cells

Toxicarioside N (Tox N), a natural product extract from Antiaris toxicaria, has been reported to induce apoptosis in human gastric cancer cells. However, the mechanism and actual role of autophagy in Tox N-induced apoptosis of human gastric cancer cells remains poorly understood. In the current study, we demonstrated that Tox N could induce autophagy by inhibiting the Akt/mTOR signaling pathway in SGC-7901 cells. Moreover, we found that the inhibition of autophagy by 3-methyladenine, an autophagy inhibitor, enhanced Tox N-induced apoptotic cell death. However, the stimulation of autophagy by rapamycin, an autophagy activator, remarkably suppressed Tox N-induced apoptosis, suggesting that autophagy plays a protective role in Tox N-induced apoptosis. Thus, the results from this study suggested that Tox N combination with an autophagy inhibitor might be a promising strategy to enhance the anticancer activity of Tox N for the treatment of human gastric cancer.     

Apoptosis initiation of β-ionone in SGC-7901 gastric carcinoma cancer cells via a PI3K-AKT pathway

β-ionone has been shown to hold potent anti-proliferative and apoptosis induction properties in vitro and in vivo. To investigate the effects of β-ionone on apoptosis initiation and its possible mechanisms of action, we qualified cell apoptosis, proteins related to apoptosis and a phosphatidylinositol 3-kinase (PI3K)—AKT pathway in human gastric adenocarcinoma cancer SGC-7901 cells. The results demonstrated that β-ionone-induced apoptosis in a dose-dependent manner in SGC-7901 cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. β-ionone was also shown to induce the expression of cleaved-caspase-3 and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner. The significantly decreased levels of p-PI3K and p-AKT expression were observed in SGC-7901 cells after β-ionone treatments in a time- and dose-dependent manner (P < 0.01). Thus, the apoptosis induction in SGC-7901 cells by β-ionone may be regulated through a PI3K-AKT pathway. These results demonstrate a potential mechanism by which β-ionone to induce apoptosis initiation in SGC-7901 cells.     

Honokiol inhibits gastric tumourigenesis by activation of 15-lipoxygenase-1 and consequent inhibition of peroxisome proliferator-activated receptor-�� and COX-2-dependent signals

Background and purpose:

Peroxisome proliferator-activated receptor-γ (PPAR-γ), COX-2 and 15-lipoxygenase (LOX)-1 have been shown to be involved in tumour growth. However, the roles of PPAR-γ, COX-2 or 15-LOX-1 in gastric tumourigenesis remain unclear. Here, we investigate the role of 15-LOX-1 induction by honokiol, a small-molecular weight natural product, in PPAR-γ and COX-2 signalling during gastric tumourigenesis.

Experimental approach:

Human gastric cancer cell lines (AGS, MKN45, N87 and SCM-1) were cultured with or without honokiol. Gene and protein expressions were analysed by RT–PCR and Western blotting respectively. Small interfering RNAs (siRNAs) for COX-2, PPAR-γ and 15-LOX-1 were used to interfere with the expressions of these genes. A xenograft gastric tumour model in mouse was used for in vivo study.

Key results:

PPAR-γ and COX-2 proteins were highly expressed in gastric cancer cells. Inhibitors, or siRNA for COX-2 or PPAR-γ, significantly decreased cell viability. Honokiol markedly inhibited PPAR-γ and COX-2 expressions in gastric cancer cells and tumours of xenograft mice, and induced apoptosis and cell death. Honokiol markedly activated cellular 15-LOX-1 expression and 13-S-hydroxyoctadecadienoic acid (a primary product of 15-LOX-1 metabolism of linoleic acid) production. 15-LOX-1 siRNA could reverse the honokiol-induced down-regulation of PPAR-γ and COX-2, and cell apoptosis. 15-LOX-1 was markedly induced in tumours of xenograft mice treated with honokiol.

Conclusions and implications:

These findings suggest that induction of 15-LOX-1-mediated down-regulation of a PPAR-γ and COX-2 pathway by honokiol may be a promising therapeutic strategy for gastric cancer.     

Dihydrotanshinone induces apoptosis of SGC7901 and MGC803 cells via activation of JNK and p38 signalling pathways

Context: Dihydrotanshinone (DHT), a natural compound from Salvia miltiorrhiza Bunge (Lamiaceae), showed higher cytotoxic potential compared with other tanshinones. Its effect and mechanism on gastric cancer have not been investigated.

Objective: This study evaluates the effects of DHT on cell proliferation and apoptosis on gastric cancer cells, and elucidates its molecular mechanisms.

Materials and methods: Human gastric cancer MGC803 and SGC7901 cells were treated with various concentrations of DHT (0–15?μM) for 24 and 48?h, and cell growth was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cell apoptosis was analysed by flow cytometry and DAPI staining. Western blots were performed to investigate changes in the level of apoptosis related genes in gastric cancer cell.

Results: DHT exhibited obvious inhibition of the survival of gastric cancer cells. The IC₅₀ values in SGC7901 and MGC803 cells were 9.14 and 5.39?μM for 24?h, respectively. Cells treated with 6?μM DHT resulted in 41.3% and 35.4% apoptotic cell fractions in SGC7901 and MGC803 cells, respectively, significantly higher than that of the control. Hallmarks of apoptosis were observed in gastric cancer cells after DHT exposure. DHT enhanced the expression levels of cleaved caspase-3, caspase-9 and poly-ADP-ribose polymerases. Furthermore, DHT increased the phosphorylation of JNK and p38 in SGC7901 and MGC803 cells.

Conclusion: DHT induced growth inhibition and apoptosis of gastric cancer cells, involving activation of caspase proteins and the JNK/p38 signaling pathway. The results indicated that DHT has a promising chemotherapeutic potential for human gastric cancer.     

Galangin induces apoptosis in gastric cancer cells via regulation of ubiquitin carboxy-terminal hydrolase isozyme L1 and glutathione S-transferase P

Galangin has been shown to have anti-cancer property against several types of cancer cells. Many studies have described the anti-oxidant and apoptotic effects of galangin. However, the mechanism of galangin-induced apoptosis has not yet been studied for human gastric cancer cells. We investigated galangin-induced apoptosis of human gastric cancer SNU-484 cells. Galangin inhibited proliferation of SNU-484 cells in a dose- and time-dependent manner. The results showed that galangin significantly decreased the viability of SNU-484 cells at 50-200 μM for 24 h and 48 h. Galangin-induced cell death was characterized with the changes in cell morphology, DNA fragmentation, cell cycle, activation of caspase-3/-9, poly (ADP-ribose) polymerase (PARP) cleavage, and expression of MAP kinase such as ERK1/2 and JNK. For identification of proteins potentially involved in apoptosis, a two-dimensional electrophoresis was employed. Proteomic analysis showed that several proteins were associated with anti-cancer properties of galangin. Of particular interest, these proteins included ubiquitin carboxy-terminal hydrolase isozyme L1 (Uch-L1) and glutathione S-transferase P (GSTP), which are involved in apoptosis of SNU-484 cells. Western blot analysis confirmed up-regulation of Uch-L1 and down-regulation of GSTP following galangin treatment. Our results suggest that Uch-L1 and GSTP be involved in galangin-induced apoptosis in human gastric cancer SNU-484 cells.     

Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells

Betulin, an abundant natural compound, significantly inhibited the cell viability of advanced human gastric cancer SGC7901 cells. Mechanism study demonstrated that betulin induced apoptosis through mitochondrial Bax and Bak accumulation-mediated intrinsic apoptosis pathway. Downregulation of the anti-apoptosis proteins Bcl-2 and XIAP was involved during betulin-induced cell apoptosis. Reactive oxygen species (ROS) was generated in cells after betulin treatment in a time- and dose-dependent manner. Addition of antioxidant N-acetyl-l-cysteine (NAC) significantly attenuated betulin-induced ROS generation as well as Bcl-2 and XIAP downregulation. The mitochondrial accumulation of Bax and Bak, as well as caspase activity, was also remarkably inhibited by NAC treatment, indicating that ROS are important signaling intermediates that lead to betulin-induced apoptosis by modulating multiple apoptosis-regulating proteins in SGC7901 cells.     

微小RNA-588靶向调控脾酪氨酸激酶的表达及其对胃癌细胞增殖、凋亡的作用

目的 探讨微小RNA-588(miR-588)对胃癌细胞增殖、凋亡的影响以及潜在的作用机制.方法 运用实时荧光定量逆转录聚合酶链式反应(qRT-PCR)检测胃癌细胞SGC-7901、BGC-823和正常胃黏膜细胞GES-1中miR-588的表达水平;将胃癌细胞SGC-7901、BGC-823分为anti-miR-NC组...     

Cerenkov luminescence imaging on evaluation of early response to chemotherapy of drug-resistant gastric cancer

Apoptosis imaging enables a timely and specific assessment of treatment response in cancer patients. In this study, we applied a probe for positron emission tomography (PET), which served as an optical biomaterial emitting Cerenkov photons, to in vivo optical imaging of tumor apoptosis, in order to evaluate early response to chemotherapy of drug-resistant gastric cancer. ⁶⁸Ga-DOTA-Annexin V was prepared as the apoptosis targeting probe. Wild type human gastric adenocarcinoma cell line SGC7901/WT and drug vincristine-resistant variant SGC7901/VCR were used to establish normal and vincristine-resistant xenografts to simulate treatment decision situation. Vincristine-resistance of SGC7901/VCR and apoptosis-induction ability of vincristine and cisplatin were verified. In vitro and in vivo CLI of apoptosis was performed. Stronger signals of apoptosis of CLI correlated with confirmed higher levels of apoptosis and subsequent changes in tumor sizes. Our study suggests that CLI is a promising technique for in vivo imaging of apoptosis with radiopharmaceutical-labeled biomaterials.     

miR-578调控长链脂酰辅酶A合成酶4表达对胃癌细胞增殖、侵袭的影响

目的 探讨miR-578调控长链脂酰辅酶A合成酶4（ACSL4）对胃癌细胞增殖及侵袭的影响。方法 选取人胃癌细胞MKN-45、SNU-1、MKN-7、KTAO3、N87及人正常胃黏膜细胞GES-1为研究对象,将MKN-45细胞分为对照组、miR-578 NC组、miR-578 mimic组、miR-578 mimic+pc-ACSL4组,测定各组MKN-45细胞活力及凋亡、侵袭、迁移能力,测定细胞中miR-578、ACSL4、凋亡相关蛋白（Bax、Caspase-3、Bcl-2）、侵袭相关蛋白（MMP-9、MMP-2）的表达,验证miR-578与ACSL4的靶向关系。结果 miR-578在人胃癌细胞中低表达;与对照组相比,miR-578 mimic组MKN-45细胞活力、侵袭、迁移能力、MMP-2、MMP-9、Bcl-2蛋白表达水平均显著降低（P<0.05）,凋亡能力、Caspase-3、Bax蛋白表达水平均显著升高（P<0.05）;与miR-578 mimic组相比,miR-578 mimic+pc-ACSL4组MKN-45细胞活力、侵袭、迁移能力、MMP-2、MMP-9、Bcl-2蛋白表达水平均显著升高（P<0.05）,凋亡能力、Caspase-3、Bax蛋白表达水平均显著降低（P<0.05）;荧光素酶实验结果显示,miR-578与ACSL4存在靶向调节关系。结论 miR-578可抑制人胃癌细胞MKN-45的增殖及迁移能力,可能是通过抑制ACSL4表达实现的。     

凋亡抑制蛋白在TRAIL诱导胃癌细胞凋亡中的作用

目的探讨凋亡抑制蛋白(inhibitor of apoptosis pro-teins,IAP)在调节胃癌细胞对肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)敏感性方面的作用。方法 PI染色流式细胞术检测细胞凋亡;Western blot检测caspase-3、PARP、XIAP、Survivin、cIAP1和cIAP2的表达。结果 TRAIL能诱导胃癌细胞凋亡,BGC-823细胞较SGC-7901细胞对TRAIL更敏感。caspase-3的活化及PARP的裂解在TRAIL作用早期即出现,且BGC-823细胞较SGC-7901细胞发生得更快。4种IAP蛋白在两株胃癌细胞中都组成性地高表达,Survivin和cIAP1在TRAIL处理前后无变化。而XIAP在BGC-823细胞中明显下降,在SGC-7901细胞中无改变。cIAP2在TRAIL作用后两株细胞中均有所降低。结论 TRAIL诱导胃癌细胞凋亡可能在活化的caspase-3水平受调控,XIAP能保护胃癌细胞免于凋亡。     

MAPK14 (p38α) inhibition effects against metastatic gastric cancer cells: A potential biomarker and pharmacological target

Gastric cancer has been considering one of the worst cancer types since it is diagnosed in advanced stages, currently in the metastatic stage. Therefore, the challenge is to find out a biomarker and a pharmacology target that would help face this worldwide health issue. In this sense, the mitogen-activated protein kinase (MAPK) signaling pathway has become an important aim of the studies in several cancers. Therefore, we evaluated the role of MAPK14 (p38α) inhibitor SB-245392 in the cellular process, such as proliferation, cell death, and cell migration, and whether MAPK14 gene could be a potential biomarker in gastric cancer models. The results clearly suggest that p38α inhibition significantly impairs the cell proliferation, induces modest apoptosis and strongly inhibits cell migration of gastric cancer cell (AGP-01). Gene expression analysis showed that c-MYC level was decreased and TP53 was increased after SB-245392 treatment. Furthermore, MAPK14 was found in high levels in gastric cancer samples compared to normal samples in the TCGA database, especially in advanced stages (stage 3 and 4), which is significantly associated with low rate survival of the patients. In conclusion, the MAPK14 could be a potential biomarker for advanced gastric cancer as well as a pharmacological target, which could improve the survival rate of patients.     

A new bisphosphonate derivative,CP, induces gastric cancer cell apoptosis via activation of the ERK1/2 signaling pathway

Aim:

To investigate the effects of a new derivative of bisphosphonates, [2-(6-aminopurine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP), on human gastric cancer.

Methods:

Human gastric cancer cell lines (SGC-7901, BGC-823, MKN-45, and MKN-28) and human colon carcinoma cell lines (LoVo and HT-29) were tested. Cell growth was determined using the MTT assay. Flow cytometry, Western blot, caspase activity assay and siRNA transfection were used to examine the mechanisms of anticancer action. Female BALB/c nude mice were implanted with SGC-7901 cells. From d6 after inoculation, the animals were injected with CP (200 μg/kg, ip) or vehicle daily for 24 d.

Results:

CP suppressed the growth of the 6 human cancer cell lines with similar IC₅₀ values (3239 μmol/L). In SGC-7901 cells, CP arrested cell cycle progression at the G₂/M phase. The compound activated caspase-9, increased the expression of pro-apoptotic proteins Bax and Bad, decreased the expression of anti-apoptotic protein Bcl-2. Furthermore, the compound selectively activated ERK1/2 without affecting JNK and p38 in SGC-7901 cells. Treatment of SGC-7901 cells with the specific ERK1/2 inhibitor PD98059 or ERK1/2 siRNA hampered CP-mediated apoptosis. In the human gastric cancer xenograft nude mouse model, chronic administration of CP significantly retarded the tumor growth.

Conclusion:

CP is a broad-spectrum inhibitor of human carcinoma cells in vitro, and it also exerts significant inhibition on gastric cancer cell growth in vivo. CP induces human gastric cancer apoptosis via activation of the ERK1/2 signaling pathway.     

BJcuL, a lectin purified from Bothrops jararacussu venom, induces apoptosis in human gastric carcinoma cells accompanied by inhibition of cell adhesion and actin cytoskeleton disassembly

We show that BJcuL, a lectin purified from Bothrops jararacussu venom, exerts cytotoxic effects to gastric carcinoma cells MKN45 and AGS. This effect was due to the direct interaction with specific glycans on the cells surface and was observed by cell viability decrease, disorganization of actin filaments and apoptosis. In addition, BJcuL was able to reduce tumor cell adhesion to matrigel, what was inhibited by specific carbohydrate or partially inhibited when cells were pre-incubated with matrigel. Our results suggest that BJcuL was able to promote apoptosis in both tumor cells lines and therefore has a prospect for potential use in cancer therapy.     

β,β-Dimethylacrylshikonin exerts antitumor activity via Notch-1 signaling pathway in vitro and in vivo

β,β-Dimethylacrylshikonin (DA) is a major component of Radix Lithospermum erythrorhizon and has various biological activities. We have investigated the inhibitory effect of DA on the growth of hepatocellular carcinoma in vitro and in vivo. Notch signaling plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis. Hence, perturbed Notch signaling may contribute to tumorigenesis. In the present study, we evaluated whether DA could be an effective inhibitor on cell growth in human gastric cancer cell line, and also the molecular mechanisms. Using multiple cellular and molecular approaches such as MTT assay, colony formation assay, DAPI staining, flow cytometry, real-time PCR and Western blot analysis, we found that DA inhibited cell growth in a dose- and time-dependent manner. Biochemical analysis revealed the involvement of cell cycle regulated proteins in DA-mediated of G₀–G₁ arrest of SGC-7901 cells. Furthermore, DA treatment led to reduced Notch-1 activation, expression of Jagged-1 and its downstream target Hes-1 in vitro and in vivo. Our data demonstrated that DA is a potent inhibitor of progression of gastric cancer cells, which could be due to attenuation of Notch-1. We also suggest that DA could be further developed as a potential therapeutic agent for the treatment of gastric cancer.     

基于网络药理学的参苓扶正方治疗胃癌生物学物质基础及药效机制研究

目的：采用网络药理学方法研究参苓扶正方治疗胃癌的生物学物质基础及其药效机制。方法：借助中药系统药理学数据库与分析平台（traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP）、GeneCards等数据库及相关文献构建参苓扶正方（主要药物为人参、半夏、黄连、茯苓、白术）治疗胃癌的"药物-疾病-靶点"网络,利用STRING及CentiScape插件构建上述药物治疗胃癌的蛋白-蛋白相互作用（protein-protein interaction,PPI）网络,同时对关键靶点进行基因本体（Gene Ontology,GO）功能富集分析以及京都基因与基因组百科全书通路富集（Kyoto Encyclopedia of Genes and Genomes,KEGG）信号通路富集分析,并以细胞实验进一步验证网络药理学所得结论。结果：参苓扶正方治疗胃癌的"药物-疾病-靶点"网络共涉及139个共同靶点,GO功能富集提示参苓扶正方治疗胃癌的生物学过程及功能集中在泛素化、核受体功能、转录相关功能、激素受体功能、细胞凋亡、细胞周期等;KEGG通路富集分析提示参苓扶正方治疗胃癌主要涉及细胞凋亡、细胞周期、肿瘤抑制信号通路（p53）、内分泌抵抗、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）、肿瘤坏死因子（TNF）等信号通路。细胞实验结果显示,参苓扶正方可有效抑制胃癌BGC-823细胞的增殖并促进其凋亡。Western blotting结果显示参苓扶正方能够调控胃癌BGC-823细胞增殖、凋亡以及细胞周期相关蛋白的表达水平。结论：参苓扶正方治疗胃癌的作用靶点和药效机制,可能与其调控细胞增殖、凋亡和细胞周期的生物学过程及信号通路相关。