Network pharmacology analysis combined with experimental verification of the molecular mechanism of Xihuang pill in treating liver cancer

Background:Xihuang pill is a kind of traditional Chinese medicine,which has been widely used in the treatment of kinds of cancer.However,there is still a lack of systematic understanding of the molecular mechanism of Xihuang pill in the treatment of liver cancer.In this work,we aim to explore the molecular mechanism of Xihuang pill in treating liver cancer.Methods:The functional components in Xihuang pill were collected from Traditional Chinese Medicine Database and Analysis Platform.The target genes of these components were also collected using Traditional Chinese Medicine Database and Analysis Platform.The target genes of liver cancer were predicted using GeneCards database.The intersecting genes were then analyzed with Venn diagrams.Kyoto Encyclopedia of Genes and Genomes and Database for Annotation,Visualization,and Integrated Discovery were used to analyze the pathway.Then,cell counting kit-8 was used to measure the half-maximal inhibitory concentration of Xihuang pills.The living dead cell staining method was used to observe the survival of cells.HepG2 cell apoptosis was tested by flow cytometry with fluorescein isothiocyanate/propidium iodide double staining method,and then the mitochondrial damage was also detected by flow cytometry.The expression of target genes was detected by quantitative real-time polymerase chain reaction.Results:A total of 130 compounds and 198 genes were identified as potential active ingredients and putative liver cancer‑related targets.We obtained 1,899 disease targets and 297 transcriptome targets from the database.Six drug-disease intersecting genes,CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3 were obtained.They are enrichment in apoptosis,PI3K-AKT signaling pathway,MAPK signaling pathway,pathways in cancer and p53 signaling pathway.Besides,it was found that the apoptosis rate of the HepG2 cells in Xihuang pill treated group was significantly higher than that of the control group.And the apoptosis rate gradually increased in a dose dependent manner of Xihuang pill treatment.Xihuang pill also induced the mitochondrial membrane potential damage.Compared with the control group,the expression level of CCNB1 and BIRC5 was induced,while the expression level of IGF2 was reduced after Xihuang pill treatment.Conclusion:Xihuang pill may act on six proteins(CCNB1,BIRC5,TOP2A,ESR1,IGF2 and IGFBP3)and cover multiple pathways to form a therapeutic network to treat liver cancer.

Xihuang pills induce apoptosis in hepatocellular carcinoma by suppressing phosphoinositide 3-kinase/protein kinase- B/mechanistic target of rapamycin pathway

BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma(HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHPassociated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway.AIM To confirm the effect of XHP on HCC and the possible mechanisms involved.METHODS The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS). Cellbased experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP(0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay.Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction(RT-qPCR), respectively.Third, Western blotting and RT–qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway.Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed.RESULTS The following 12 compounds were identified in XHP using high-resolution mass spectrometry:Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-β-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-β-boswellic acid, 5β-androstane-3,17-dione, and 3-acetyl-11-keto-β-boswellic acid. The cell viability assay results showed that treatment with 0.625mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose-and timedependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract(0.625mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins(e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights.CONCLUSION XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3.Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.

西黄丸抑制乳腺癌4T1荷瘤小鼠生长的作用及其机制

目的:观察西黄丸抑制4T1荷瘤小鼠生长的作用及其免疫调控机制。方法:建立4T1小鼠乳腺癌模型,观察不同剂量西黄丸干预对肿瘤生长的抑制作用;流式细胞仪检测荷瘤小鼠外周血、脾脏、骨髓来源免疫抑制细胞(myeloid-derived suppressor cells,MDSCs)比例,同时分离小鼠脾脏检测活性氧(reactive oxygen species,ROS)、CD3+T、CD8+T、CD8+T IFN-γ+细胞所占的比例;Luminex液相芯片技术检测荷瘤小鼠外周血白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、单核细胞趋化因子-1(monocyte chemoattractant protein-1,MCP-1)的含量。结果:西黄丸0.9、0.6、0.3 g/kg各剂量治疗组均显示了一定的抑制肿瘤生长的作用(P<0.01或P<0.05),其中以0.9 g/kg组抑制作用最为明显,抑瘤率达到40%。西黄丸可减少荷瘤小鼠外周血、骨髓、脾脏MDSCs比例以及脾脏细胞ROS水平,提高脾脏细胞CD3+T细胞、CD8+T以及CD8+T IFN-γ+细胞所占的比例,同时,西黄丸可显著减少小鼠外周血MDSCs生成密切相关细胞因子IL-6、IL-1β的表达。结论:西黄丸可通过减少MDSCs比例,增强荷瘤小鼠抗肿瘤免疫功能抑制小鼠4T1炎性乳腺癌的生长,降低IL-6、IL-1β可能是其调控MDSCs的机制之一,对于其深入的作用机制还需要进一步的探索。

西黄胶囊联合藤药外敷治疗盆腔炎性包块的应用效果

目的探讨西黄胶囊联合藤药外敷治疗盆腔炎性包块的应用效果。方法选取2020年12月至2022年8月江西省妇幼保健院收治的60例盆腔炎性包块患者作为研究对象,采用随机数字表法将其分成对照组(30例)与试验组(30例),对照组行单纯藤药外敷治疗,试验组在此基础上加用西黄胶囊。比较两组患者临床疗效、中医症状积分与包块直径大小。结果试验组治疗总有效率高于对照组,差异有统计学意义(P<0.05)。试验组治疗后腰骶酸痛、下腹坠痛或刺痛、带下量多、月经失调、神疲乏力、低热的症状积分均低于对照组,差异有统计学意义(P<0.05)。试验组治疗后的包块直径小于对照组,差异有统计学意义(P<0.05)。结论西黄胶囊联合藤药外敷治疗盆腔炎性包块患者,效果好,能显著改善症状,并能缩小包块,综合效能高。

西黄胶囊联合西妥昔单抗通过Nrf2/HO-1信号通路调控结直肠癌细胞凋亡、迁移以及侵袭的作用机制研究

目的研究西黄胶囊联合西妥昔单抗通过Nrf2/HO-1信号通路对结直肠癌细胞凋亡、迁移以及侵袭的调控作用。方法使用细胞计数试剂盒(CCK8)确定西黄胶囊和西妥昔单抗对结直肠癌HCT-116细胞活力的影响。使用流式细胞术、划痕法和侵袭小室法检测西黄胶囊联合西妥昔单抗对结直肠癌HCT-116细胞凋亡、迁移以及侵袭的影响。使用蛋白质印迹技术检测西黄胶囊联合西妥昔单抗对结直肠癌HCT-116细胞B细胞淋巴瘤2(BCL2)、BCL2关联X蛋白(BAX)、基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)、锌指蛋白232(ZNF320)、血管内皮生长因子A(VEGA)、糖原合成酶激酶3β(GSK3β)、核因子E2相关因子2(NRF2)和血红素氧合酶1(HO-1)表达的影响。结果CCK8实验结果显示,西黄胶囊和西妥昔单抗对HCT-116细胞活力最佳抑制时间是72 h,IC 50分别为5.28%和170.20 mg/L。与对照组相比,西黄胶囊和西妥昔单抗增加HCT-116细胞的凋亡(P<0.05)、抑制HCT-116细胞迁移以及侵袭(P<0.05)。与单独使用西黄胶囊或西妥昔单抗相比,西黄胶囊联合西妥昔单抗对HCT-116细胞的促凋亡效果和对迁移以及侵袭的抑制效果更加明显(P<0.05)。蛋白质印迹技术结果显示,与对照组比较,西黄胶囊和西妥昔单抗促进HCT-116细胞的BAX表达(P<0.05),抑制BCL2、MMP2、MMP9、ZNF320、VEGA、GSK3B、NRF2、HO-1的表达(P<0.05)。此外,与单独使用西黄胶囊或西妥昔单抗相比,西黄胶囊联合西妥昔单抗的效果更加明显(P<0.05)。结论西黄胶囊联合西妥昔单抗可能通过抑制Nrf2/HO-1信号通路抑制结直肠癌HCT-116细胞的活力、迁移以及侵袭,促进细胞凋亡,且西黄胶囊联合西妥昔单抗的干预效果优于单独使用西黄胶囊或西妥昔单抗。

复方苦参注射液联合西黄丸对晚期结直肠癌姑息治疗患者癌性疼痛和疲乏中位生存期及并发症发生率影响

目的:探讨复方苦参注射液联合西黄丸对晚期结直肠癌姑息治疗患者癌性疼痛和疲乏、中位生存期及并发症发生率影响。方法:将2020年1月至2021年5月成都医学院第一附属医院收治的153例晚期结直肠癌患者随机分为对照组(常规姑息治疗)、单药组(常规姑息治疗+西黄丸)、联合组(常规姑息治疗+西黄丸+复方苦参注射液),各51例。比较三组治疗前、治疗1个周期及治疗3个周期后癌性疼痛[疼痛数字分级法(NRS)]、癌因性疲乏[Piper疲乏修订量表(PFS-R)]、生存情况[功能状态评分(KPS)]评分、炎症因子[白细胞介素-6(IL-6)、C反应蛋白(CRP)、IL-8、IL-1β]、免疫功能(总T淋巴细胞、总B淋巴细胞、NK细胞),并比较三组肿瘤控制效果、并发症、毒副反应及中位生存期。结果:联合组肿瘤稳定占比高于对照组、单药组,且单药组高于对照组,进展患者占比低于单药组、对照组,且单药组低于对照组(P<0.05);联合组治疗1个、3个周期后NRS评分、PFS-R评分低于单药组、对照组,且单药组低于对照组,KPS评分高于单药组、对照组,且单药组高于对照组(P<0.05);联合组治疗1个、3个周期后总T淋巴细胞、总B淋巴细胞、NK细胞高于单药组、对照组,且单药组高于对照组(P<0.05);联合组治疗1个、3个周期后IL-6、CRP、IL-8、IL-1β低于单药组、对照组,且单药组低于对照组(P<0.05);联合组便秘、失眠、肠梗阻、肠出血、低热、感染发生率低于单药组、对照组,单药组便秘、失眠、肠梗阻、低热、感染发生率低于对照组(P<0.05);联合组恶心呕吐、骨髓抑制发生率低于单药组、对照组,且单药组低于对照组(P<0.05);随访2年,均失访2例,联合组死亡7例,单药组死亡20例,对照组死亡34例。联合组、单药组、对照组中位生存期分别为18、14、13个月,联合组中位生存期长于单药组、对照组(P<0.05)。结论:复方苦参注射液联合西黄丸可有效减轻晚期结直肠癌姑息治疗患者癌性疼痛和疲乏,改善患者生存质量,提高免疫功能,降低炎症反应及并发症发生率。

西黄丸抑制肝癌细胞增殖和转移的作用及机制研究

为了考察中药制剂西黄丸(Xihuang Pill)对肝癌细胞的作用及对Yes相关蛋白/具有PDZ结合基序的转录共激活因子(Yes-associated protein/transcriptional co-activator with PDZ-binding motif,YAP/TAZ)信号通路的影响,在SD大鼠中利用灌胃给药和动脉采血技术,制备西黄丸含药血清;利用磺酰罗丹明B(sulforhodamine B,SRB)染色技术,检测西黄丸含药血清对肝癌细胞增殖能力和克隆形成能力的影响;利用流式细胞术和原位末端转移酶标记(terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling,TUNEL)技术,检测西黄丸含药血清对肝癌细胞凋亡的影响;利用小室迁移测定实验模型,检测西黄丸含药血清对肝癌细胞侵袭和迁移能力的影响;利用小鼠肿瘤细胞异种移植模型,检测西黄丸对肝癌细胞体内增殖能力的影响;利用蛋白质印迹技术和荧光定量PCR技术,检测西黄丸含药血清对YAP/TAZ信号通路相关蛋白质和基因表达的影响。体外结果显示,西黄丸含药血清显著抑制肝癌细胞的体外增殖、克隆形成、侵袭和迁移能力,显著促进肝癌细胞的凋亡,显著抑制YAP/TAZ信号通路相关蛋白质和基因的表达,且具有剂量依赖性。体内结果显示,西黄丸显著抑制肝癌细胞的体内增殖能力,且具有剂量依赖性。研究结果提示,西黄丸能抑制肝癌细胞的体内外增殖、侵袭和转移能力,并可能在YAP/TAZ信号通路中发挥作用。

揿针联合西黄丸治疗实证肝癌化疗栓塞术后临床观察

目的:对揿针联合西黄丸治疗实证肝癌化疗栓塞术后的临床疗效进行观察研究。方法:将某院就诊的原发性肝癌患者随机分为对照组和观察组,各48例。对照组采用三阶梯药物止痛法治疗,观察组在对照组治疗的基础上给予揿针联合西黄丸治疗,比较两组患者治疗前后的腹痛(VAS)评分、中医证候积分、生活质量(KPS)评分以及血清AFP和GAS水平。结果:观察组总有效率为95.83%,显著高于对照组的89.58%(P<0.05);治疗后观察组中医证候积分、腹痛评分以及AFP水平均显著低于对照组和治疗前(P<0.05),生活质量KPS评分以及血清GAS水平显著高于对照组和治疗前(P<0.05)。结论:揿针联合西黄丸治疗实证肝癌腹痛患者疗效显著,可显著降低患者的疼痛评分,提高患者生活质量,值得临床推广应用。

中医经典名方西黄丸处方考证、历史沿革应用及其质量标志物预测分析

经典名方西黄丸出自《外科证治全生集·卷四》,为清代名医王洪绪所创,是中医治疗乳腺癌的经典方剂,由牛黄、麝香、乳香、没药4味药物组成。功效清热解毒、消肿散结,主治热毒壅结所致痈疽疔毒、瘰疬、流注、癌肿,临床常用于治疗肺癌、乳腺癌、胃癌等,在肿瘤辅助治疗方面疗效显著。该文通过医药典籍系统梳理该处方的出处,对处方用量、处方中各药味进行了考证,并对西黄丸的历史沿革应用进行分析,同时以质量标志物(Q-Marker)的“五原则”为纲领预测了西黄丸的质量标志物,结果发现麝香酮、α-乳香酸、β-乳香酸、3-乙酰基-11-酮基-β-乳香酸、3-乙酰基-α-乳香酸、3-乙酰基-β-乳香酸、11-酮基-β-乳香酸、β-榄香烯等可作为西黄丸主要的Q-Marker,为西黄丸的质量控制、后续的研究开发以及临床应用提供了科学的理论依据。

西黄胶囊联合XP方案治疗晚期胃癌的近期疗效及对外周血肿瘤标志物、细胞免疫功能和血管生成调节因子的影响

目的:探讨西黄胶囊联合卡培他滨+顺铂(XP方案)治疗晚期胃癌的近期疗效及其对患者外周血肿瘤标志物、细胞免疫功能和血管生成调节因子水平的影响。方法:选择2019年1月至2022年3月北京航天总医院收治的晚期胃癌患者152例,以随机数字表法分为观察组和对照组,每组76例。对照组患者给予XP方案治疗,观察组患者在对照组的基础上联合西黄胶囊治疗,21 d为1个疗程。连续治疗4个疗程后进行近期疗效评价,治疗过程中记录两组患者的不良反应情况。治疗前后检测两组患者血清肿瘤标志物[糖类抗原(CA)19-9、CA72-4和癌胚抗原(CEA)]、细胞免疫功能[外周血CD3^(+)、CD4^(+)、CD8^(+)T细胞百分比和CD4^(+)/CD8^(+)比值]及血清血管生成调节因子[血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和转化生长因子-β1(TGF-β1)]水平,并随访记录两组患者的远期生存情况。结果:观察组患者的客观缓解率、疾病控制率分别为51.32%(39/76)、93.42%(71/76),显著高于对照组的30.26%(23/76)、82.89%(63/76),差异均有统计学意义(P<0.05)。观察组患者白细胞减少、血小板减少和胃肠道反应的发生率显著低于对照组,差异均有统计学意义(P<0.05)。治疗后,两组患者CA19-9、CA72-4和CEA,VEGF、bFGF和TGF-β1水平均较治疗前显著降低,观察组患者较对照组降低更为显著,差异均有统计学意义(P<0.05)。治疗后,观察组患者外周血CD3^(+)、CD4^(+)水平及CD4^(+)/CD8^(+)比值均较治疗前显著升高,且显著高于对照组,差异均有统计学意义(P<0.05)。观察组患者中位无进展生存期、中位总生存期分别为6.1、12.9个月,均较对照组(4.7、9.8个月)显著延长,差异均有统计学意义(P<0.05)。结论:西黄胶囊联合XP方案治疗晚期胃癌患者,能有效抑制血清肿瘤标志物水平,调控血管生成调节因子的表达,改善机体细胞免疫功能,提高近期疗效及远期生存获益,且表现出一定的减毒作用。

西黄丸辅助白蛋白结合型紫杉醇联合环磷酰胺化疗对乳腺癌患者免疫功能的影响

目的:观察西黄丸辅助白蛋白结合型紫杉醇联合环磷酰胺(TC)化疗方案对乳腺癌患者术后免疫功能的影响。方法:选取2021年1月1日~2023年5月1日某院甲乳外科收治的78例乳腺癌术后行TC化疗方案的患者为研究对象,采用随机数字表法分为对照组和观察组,每组39例。对照组给予TC化疗方案进行治疗,观察组在对照组治疗基础上加用西黄丸。治疗2个周期后,比较两组患者免疫指标[CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、自然杀伤(NK)细胞]水平变化。结果:治疗后,观察组CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、NK细胞水平均高于对照组(P<0.05),CD8^(+)水平低于对照组(P<0.05)。结论:西黄丸辅助TC化疗可通过调节CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、NK细胞水平,改善行TC化疗的乳腺癌患者术后免疫功能,建议临床推广。

Xihuang Pill(西黄丸) Induces Mesenchymal-Epithelial Transition and Inhibits Loss of Apical-Basal Polarity in Colorectal Cancer Cell through Regulating ZEB1-SCRIB Loop

Objective：To investigate the antiproliferative and anti-metastasis effect of Xihuang Pill（西黄丸,XP） on human colorectal cancer cell and to explore the molecular mechanism by which it produces the effects.Methods：Highly metastatic human colorectal cancer cell line LoVo was treated with low-,medium-,and highdose XP-containing serum（XP-L,XP-M,XP-H） groups for 48 h,cells intervened with no drug rat serum and PD98059[extracellular signal-regulated kinase（ERK） inhibitor]as negative and positive controls（NC and PC）groups.Cell proliferation assay was made using cell counting kit-8（CCK8）.The 8 μm pore-size transwell chamber and 4＇,6-diamidino-2-phenylindole（DAPI） staining were applied to examine the ability of invasion and migration of the cells.The protein expression of ERK1/2,zinc finger E-box-binding homeobox 1（ZEB1）,Scrib and lethal giant larvae homolog 2（Lgl2） was detected by Western blotting while the relative mRNA quantity of E-cadherin,N-cadherin,Occludin and junctional adhesion molecule-1（JAM1） was measured by realtime fluorescent quantitative polymerase chain reaction（RT-qPCR）.Results：XP induced a dose-dependent suppression on the proliferation of LoVo cells（P〈0.05 or P〈0.01）,with the inhibition rates varied from 27.30%to31.08%.Transwell assay showed that when preprocessed with PD98059 and XP-containing serum,the number of cells that passed the filter decreased significantly compared with that of NC group（P〈0.05 or P〈0.01）.Moreover,XP inhibited the protein expression of ERK1/2 and ZEB1（P〈0.05）;and up-regulated the protein expression of Scrib and Lgl2（P〈0.05）.The mRNA levels of E-cadherin,Occludin and JAM1 of the XP intervened groups and PC group markedly ascended（P〈0.05） while that of N-cadherin showed a descending tendency（P〉0.05）.Conclusion：XP intervention suppressed the ability of proliferation,invasion and migration of the LoVo cells.Regulating ZEB1-SCRIB Loop so as to recover epithelial phenotype and apical junctional complex might be one of the mechanisms by which XP produces the anti-metastasis effect.

基于定量蛋白质组学探讨西黄丸抗乳腺增生的作用机制

目的基于定量蛋白质组学技术明确西黄丸抗乳腺增生(hyperplasia of mammary glands,HMG)中乳腺组织的差异蛋白并验证,探讨其作用机制。方法将SD大鼠随机分为空白组、模型组和西黄丸组,每组10只。除空白组外,肌注雌孕激素建立HMG大鼠模型,为期30 d。给药西黄丸14 d后,观察各组大鼠表观形态变化,HE染色观察乳腺组织病理改变,定量蛋白质组学技术筛选各组差异表达蛋白(differentially expressed proteins,DEPs),并进行生物信息学分析和Western blot验证。结果与模型组比较,西黄丸组表观病理形态明显改善,大鼠乳头高度直径明显降低(P<0.01),组织病理程度明显缓解。定量蛋白质组学鉴定出乳腺组织4299个DEPs,对西黄丸组与空白组相对模型组变化一致的14个DEPs进行生物信息学分析,发现与肌肉系统过程的调节、肌肉收缩调节、DNA复制和DNA复制启动前过程有关。Western blot结果表明,与模型组比较,西黄丸组大鼠乳腺组织ACLY与ALDOC蛋白表达水平明显降低,BIN1蛋白表达水平明显增加(P<0.01)。结论西黄丸可能通过调控BIN1、ACLY及ALDOC蛋白水平,调控DNA复制、DNA复制启动前和肌肉系统过程的调节、肌肉收缩调节等途径发挥抗HMG作用。

Anti-breast cancer effects and mechanisms of Xihuang pill on human breast cancer cell lines

OBJECTIVE： To investigate the anti-breast cancer （BC） effects and mechanisms of action of Xihuang pill （XHP） by conducting in vitro experiments on hu- man BC cell lines. METHODS： Two human BC cell lines （MCF-7 and MDA- MB231） were cultured and treated with XHP. Cell viability was detected using the 3-（4, 5-Dimeth- ylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay. Flow cytometry was used to measure the cell cycle and apoptosis. The cell cycle was ana- lyzed with propidium iodide staining. Apoptosis was evaluated using the Annexin V-fluorescein iso- thiocyanate/propidium iodide method. Western blotting was used to analyze the expression of es- trogen receptor （ER）-α and ER-13.RESULTS： XHP had growth-inhibitory effects on MCF-7 and MDA-MB231 cells with a half-maximal inhibitory concentration （IC50） of 10.14 mg/mL （MCF-7） and 8.98 mg/mL （MDA-MB231）. Apoptosis was induced to some extent. Certain changes in the ER were caused. Upregulation of ER-a protein was found in MCF-7 cells. ER-β expression in MDA-MB231 cells was increased. Cell-cycle arrest was not observed in the two BC cell lines. ER-β ex- pression in MCF-7 cells was unchanged. No ER-a ex- pression was shown in MDA-MB231 cells. CONCLUSION： These data suggest that XHP can af- fect cell viability and cause apoptosis, but that the cell cycle is not blocked. XHP has a certain impact on ER expression, but its mechanisms of action of anti-13C effects may not be due to regulation of ER expression.

基于网络药理学探讨西黄解毒胶囊抑制三阴性乳腺癌生长与转移的机制及实验验证

目的通过网络药理学的方法探索西黄解毒胶囊抗三阴性乳腺癌(TNBC)的机制,并通过体内和体外实验进行验证。方法通过检索中草药系统药理学平台(TCMSP)数据库和查阅文献,获得西黄解毒胶囊中所含药物的有效活性成分,并在靶点筛选栏和SwissTargetPrediction数据库筛选活性成分对应的人类基因靶点。将药物靶点与在GEO数据库(GSE38959)中获得的TNBC差异表达基因相映射取交集,获得西黄解毒胶囊治疗TNBC的靶点,将交集靶点导入String在线数据库构建PPI网络,根据度值筛选西黄解毒胶囊治疗TNBC的核心靶点,在DAVID数据库对西黄解毒胶囊治疗TNBC的核心靶点进行GO和KEGG富集分析,以探索西黄解毒胶囊治疗TNBC的可能机制。在体内和体外分别采用蛋白免疫印迹和荧光定量PCR实验检测信号通路上关键信号分子的表达情况。结果网络药理学部分获得西黄解毒胶囊抗TNBC的核心靶点有HIF1A、VEGFA等,生物过程主要涉及信号转导、转录调控、增殖调节等,参与的信号通路主要有癌症信号通路、PI3K-Akt信号通路、NF-κB信号通路等。实验部分发现西黄解毒胶囊能抑制4T1细胞和移植瘤中EGFR、AKT(pan)、p-AKT(Ser473)、NF-κBp65、p-NF-κBp65、PI3Kp85、PI3Kp110α蛋白的表达,基因层面荧光定量PCR试验得出一致得结果。结论西黄解毒胶囊可能通过抑制PI3K/AKT/NF-κB信号通路发挥抗TNBC的作用。

西黄丸联合含铂方案治疗肝郁气滞型乳腺癌临床观察

目的探究西黄丸联合含铂方案治疗肝郁气滞型乳腺癌的临床疗效。方法选取2021年6月—2022年6月洛阳市中医院收治的肝郁气滞型乳腺癌患者106例,按随机数字表法分为对照组和研究组,各53例。对照组选用卡铂方案化疗,研究组联用西黄丸。比较2组治疗效果。结果研究组治疗后总有效率、KPS评分、血清癌胚抗原(CEA)水平、免疫因子水平、总不良反应率、生存质量均优于对照组(P<0.05)。结论西黄丸联合含铂方案可有效改善肝郁气滞型乳腺癌患者生存质量和免疫功能,降低肿瘤标志物表达水平和不良反应风险,临床疗效和安全性更高。

岭南文人赵希璜的罗浮山诗歌书写

赵希璜是清中叶成就杰出的岭南文人。从赵希璜生平及其《四百三十二峰草堂诗钞》可知,他将罗浮山视为其精神归宿,写下了100余首罗浮山诗歌,主要内容为探寻山水,品鉴风物和思念家乡。因受到罗浮山佛道文化浸润,加上“烟霞癖”的个人气质,又仰慕苏轼,承袭岭南诗派传统,赵希璜的罗浮山诗歌书写呈现出佛道交融的诗歌风格、清新自然的诗歌语言、豪放雄直的诗歌根柢三方面特点。

西黄胶囊联合常规四联抗结核方案治疗颈淋巴结结核临床观察

目的探讨西黄胶囊联合常规四联抗结核方案治疗颈淋巴结结核的临床疗效。方法选取医院2022年1月至12月收治的颈淋巴结结核患者56例,按治疗方法的不同分为观察组和对照组,各28例。两组均予常规四联抗结核治疗(乙胺丁醇+利福平+异烟肼+吡嗪酰胺),观察组患者加服西黄胶囊。两组患者均持续治疗6个月。结果观察组总有效率为96.43%,显著高于对照组的75.00%(P<0.05)。治疗后,观察组患者的CD_(4)^(+)T淋巴细胞水平及CD_(4)^(+)/CD_(3)^(+)显著高于对照组,CD_(3)^(+)T淋巴细胞水平显著低于对照组(P<0.05);观察组患者的白细胞介素1、白细胞介素6、肿瘤坏死因子-α水平均显著低于对照组(P<0.05)。观察组不良反应发生率为10.71%,与对照组的3.57%相当(P>0.05)。结论西黄胶囊联合常规四联抗结核方案治疗颈淋巴结结核,可改善患者的免疫功能,降低炎性因子水平。

西黄丸联合免疫及EC化疗一线治疗广泛期小细胞肺癌的临床效果及安全性

目的探讨西黄丸联合免疫及EC化疗一线治疗广泛期小细胞肺癌的临床效果及安全性。方法选取2021年8月至2023年2月江西省胸科医院收治的126例广泛期小细胞肺癌患者作为研究对象,按照随机信封法分为研究组和对照组,每组63例。对照组患者采用免疫及EC化疗,研究组在对照组的基础上联用西黄丸,比较两组患者的临床疗效、血钠浓度、胃泌素释放肽前体(proGRP)、肿瘤标志物、生存质量、不良反应发生情况。结果研究组治疗客观缓解率(ORR)高于对照组,差异有统计学意义(P<0.05)。治疗结束后7 d,两组患者肿瘤卡氏评分(KPS)高于本组治疗前,且研究组KPS评分高于对照组,差异有统计学意义(P<0.05)。研究组无进展生存期(PFS)高于对照组,差异有统计学意义(P<0.05)。治疗结束后7 d,两组患者血钠浓度高于本组治疗前,proGRP、癌胚抗原(CEA)、神经元烯醇化酶(NSE)和糖类抗原125(CA125)水平低于本组治疗前,且研究组血钠浓度高于对照组,proGRP、CEA、NSE和CA125水平低于对照组,差异有统计学意义(P<0.05)。研究组不良反应总发生率低于对照组,差异有统计学意义(P<0.05)。结论西黄丸联合免疫及EC化疗方案治疗广泛期小细胞肺癌有效率高,能够延缓肿瘤进展,降低肿瘤标志物表达水平,改善生存质量,治疗安全性和实用性较高。

西黄丸溶出度测定及不同制丸方法比较

目的建立西黄丸溶出度测定方法,比较泛制法与塑制法2种生产工艺溶出曲线的相似性,对泛制法与塑制法工艺样品进行一致性评价。方法通过筛选4种溶出介质、3种转速及2种测定方法,最终确定pH 1.2盐酸为溶出介质,转速为100 r·min^(-1),溶出方法为小杯法,溶出样品和介质的体积比为3 g/200 mL;同时,分别测定西黄丸泛制法与塑制法中胆红素的溶出度,采用非模型依赖法中的差异因子(f1)、相似因子(f2)对溶出曲线的相似性进行评价。结果在90 min时,产品的溶出率达到最高;按确定的溶出试验参数,以胆红素含量为评价指标进行精密度、重复性、稳定性等方法学考察,结果均符合要求;且2种生产工艺样品中胆红素溶出曲线的相似度良好。结论泛制法与塑制法生产工艺对产品质量无明显影响,产品质量具有一致性。