Retracted: Ganoderic acid A alleviates hypoxia‐induced apoptosis,autophagy, and inflammation in rat neural stem cells through the PI3K/AKT/mTOR pathways

Effects of ganoderic acid A (GAA), a lanostane triterpene, on hypoxia‐ischemia encephalopathy (HIE) remain unclear. We aimed to figure out the specific role of GAA in hypoxia‐treated neural stem cells (NSCs) as well as the regulatory mechanisms. Primary rat NSCs were incubated under hypoxia to simulate HIE. Viability and apoptosis of hypoxia‐injured NSCs were measured by cell counting kit‐8 and flow cytometry assays, respectively. Proteins related to apoptosis, autophagy, and the PI3K/AKT/mTOR pathways were evaluated by Western blot analysis. LY294002 and rapamycin were added to inhibit the PI3K/AKT pathway and mTOR pathway, respectively. Enzyme‐linked immunosorbent assay was carried out to test the release of proinflammatory cytokines. We found that hypoxia‐induced decrease of cell viability, increases of apoptotic cells and autophagy, and the release of IL‐6, IL‐1β, and TNF‐α were all attenuated by GAA stimulation. Activation of caspases induced by hypoxia was alleviated by GAA. Furthermore, we found that inhibition of the PI3K/AKT pathway eliminated the effects of GAA on apoptosis and proinflammatory cytokines release in hypoxia‐injured NSCs. Meanwhile, inhibition of the mTOR pathway abrogated the effects of GAA on cell autophagy in hypoxia‐injured NSCs. In conclusion, GAA alleviated hypoxia‐induced injury in NSCs might be through activating the PI3K/AKT and mTOR pathways.     

乌索酸调节PI3K/AKT/mTOR信号通路在结直肠癌中的研究进展

乌索酸（Ursolic acid,UA）是一种广泛存在于植物的草、叶、花和果实中的具有抗氧化,抗菌,抗炎,肝保护,免疫调节,抗肿瘤,化学预防,心脏保护、抗高脂血症和降低血糖等活性的五环三萜类化合物。本文综述了乌索酸结构与抗肿瘤机制、PI3K/AKT/mTOR信号通路参与结直肠癌进程以及乌索酸调节PI3K/AKT信号通路阻碍结直肠癌进展。     

Brassinin Induces Apoptosis in PC‐3 Human Prostate Cancer Cells through the Suppression of PI3K/Akt/mTOR/S6K1 Signaling Cascades

The oncogenic PI3K/Akt/mammalian target of rapamycin (mTOR) signaling axis and its downstream effector, the ribosomal protein S6 kinase 1 (S6K1) play a key role in mediating cell survival in various tumor cells. Here, we investigated the effects of brassinin (BSN), a phytoalexin first identified as a constituent of cabbage, on the PI3K/Akt/mTOR/S6K1 activation, cellular proliferation, and apoptosis in PC‐3 human prostate cancer. BSN exerted a significant dose‐dependent cytotoxicity and reduced constitutive phosphorylation of Akt against androgen‐independent PC‐3 cells as compared to androgen‐dependent LNCaP cells. Moreover, knockdown of androgen receptor (AR) by small interfering RNA enhanced the potential effect of BSN on induction of apoptosis in LNCaP cells. BSN clearly suppressed the constitutive activation of PI3K/Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, TUNEL staining, loss of mitochondrial membrane potential, down‐regulation of antiapoptotic and proliferative proteins, activation of caspase‐3, and cleavage of PARP. Additionally, BSN could block broad‐spectrum inhibition of PI3K/Akt/mTOR/S6K1 axes, and aberrant Akt activation by pcDNA3‐myr‐HA‐Akt1 plasmid could not prevent the observed suppressive effect of BSN on constitutive mTOR activation. Finally, overexpression of Bcl‐2 also attenuated BSN‐mediated apoptosis in PC‐3 cells. Taken together, our findings suggest that BSN can interfere with multiple signaling cascades involved in tumorigenesis and might be provided as a potential therapeutic candidate for both the prevention and treatment of prostate cancer. Copyright © 2013 John Wiley & Sons, Ltd.     

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??OBJECTIVE To investigate the mechanism of nucleophosmin (NPM) in the formation of breast cancer drug resistance. METHODS The methotrexate- resistant breast cancer cells (MCF-7/MTX) was established by escalating the concentrations of methotrexate to drug-sensitive MCF-7 cells (MCF-7/S). The cells viability of MCF-7/MTX was detected by MTT test, cell growth curve was drawn and doubling time was calculated. The cell morphology and ultrastructure were observed using optical and transmission electron microscopy. The expression of NPM and factors related to drug resistance were tested by Real-time PCR and Western blot assay. Then the NPM level was attenuated by RNA interfering technology, and the resistance mechanism was explored in MCF-7/MTX cells. RESULTS The MCF-7/MTX cell line was successfully established and resistance factor was 64. The resistant cells has spindle shaped morphology and tended to grow slowly, and the variations appeared in the internal structure of cells. MCF-7/MTX cells possessed cross-resistance to various chemotherapeutic drugs. The expressions of NPM and multidrug-resistant factors P-gp, MRP1, BCRP were up-regulated in the resistant cells. Further, the overexpression of NPM activated PI3K/Akt signaling pathway and inhibited downstream apoptotic factors. Then knockdown of NPM by siRNA significantly decreased the drug resistance of MCF-7/MTX cells, suppressed PI3K/Akt pathway and promoted the downstream cells apoptosis. CONCLUSION The high expression of NPM has an important role in the formation of breast cancer drug resistance, and it is expected to be a novel molecular target for breast cancer treatment in clinical.     

蠲痛饮对子宫内膜异位症大鼠PI3K/Akt/mTOR信号通路蛋白的影响

目的:探讨蠲痛饮对子宫内膜异位症(EMS)大鼠磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素靶分子(mTOR)信号通路蛋白的影响。方法:采用自体子宫内膜移植法建立EMS大鼠模型,随机将48只大鼠分为正常组、模型组、蠲痛饮低、中、高剂量组、通路阻滞剂组(LY294002) 6组,分别给予蠲痛饮高、中、低剂量(42. 9,14. 3,4. 8 g·kg~(-1))灌胃,通路阻滞剂组予PI3K通路阻滞剂LY294002(0. 04 g·kg~(-1))腹腔注射,正常组及模型组每天按照10 mL·kg~(-1)给予生理盐水灌胃,各组持续用药28 d。应用透射电镜观察大鼠异位内膜组织超微结构,免疫组化法检测异位内膜组织PI3K,Akt,mTOR蛋白表达,实时荧光定量聚合酶链式反应(Real-time PCR)检测核糖体蛋白S6激酶(p70S6K) mRNA相对含量。结果:与正常组比较,模型组异位内膜PI3K,Akt,mTOR蛋白和p70S6K mRNA的表达都明显升高(P 0. 05);与模型组比较,蠲痛饮中、高剂量、通路阻滞剂组干预后PI3K,Akt,mTOR蛋白和p70S6K mRNA的表达明显降低(P 0. 05)。透射电镜下可见蠲痛饮低、中、高剂量组和通路阻滞剂组均能促进腺上皮细胞萎缩或欠整齐,微绒毛减少或消失,胞核固缩,胞内线粒体肿胀或减少,间质细胞凋亡。结论:PI3K/Akt/mTOR信号通路参与子宫内膜异位症发生;蠲痛饮可能通过下调PI3K/Akt/mTOR通路蛋白的表达及p70S6K mRNA表达,从而抑制上皮间质细胞活性,促进细胞凋亡,治疗子宫内膜异位症。     

基于网络药理学探析参桃软肝丸治疗肝细胞癌的机制＊

目的 利用网络药理学探析参桃软肝丸治疗肝细胞癌（hepatocellular carcinoma，HCC）的机制。方法 从中药系统药理学分析平台收集组方药物的活性成分及靶点，与Genecards网站收集的HCC靶点取交集后，筛选出参桃软肝丸治疗HCC的潜在靶点，进而绘制中药-活性成分-靶点网络图并分析其关键成分，构建靶蛋白互作网络并分析其关键靶点，并进行基因本体分子功能和京都基因与基因组百科全书通路富集分析，最后通过分子对接探讨关键成分与关键靶点的相互作用。结果 参桃软肝丸治疗HCC的关键成分或为槲皮素、木犀草素、山奈酚，关键靶点或为蛋白激酶B、半胱氨酸天冬氨酸蛋白酶3、血管内皮生长因子A、V-Jun肉瘤病毒癌基因同源物、V-MYC骨髓细胞瘤病毒癌基因同源物，其作用机制或与乙型肝炎、丙型肝炎、磷脂酰肌醇3激酶/蛋白激酶B信号通路、p53信号通路、癌症中微小RNA、细胞程序性死亡配体1表达和细胞程序性死亡蛋白1检查点途径、细胞凋亡、低氧诱导因子-1信号通路、白介素-17信号通路、叉头框转录因子O信号通路有关。分子对接表明AKT1蛋白与木犀草素结合能力最强。结论 本文表明参桃软肝丸治疗HCC多靶点、多通路的作用机制，可为今后阐明参桃软肝丸治疗HCC的具体机制提供思路。     

红花多糖通过阻断PI3K/Akt/mTOR通路诱导人乳腺癌MDA-MB-435细胞凋亡的机制研究

目的研究红花多糖通过阻断PI3K/Akt/mTOR通路诱导人乳腺癌MDA-MB-435细胞凋亡的作用及其作用机制。方法将MDA-MB-435细胞分为对照组和红花多糖0.5、1.0 mg/mL组。MTT法及流式检测仪分别检测不同质量浓度红花多糖对MDA-MB-435细胞生长及凋亡的影响;RT-PCR及Western blotting法分别检测不同质量浓度红花多糖对MDA-MB-435细胞PI3K、Akt、mTOR mRNA和蛋白表达的影响。结果与对照组比较,红花多糖0.5 mg/mL组MDA-MB-435细胞抑制率为(21.52±2.43)%,红花多糖1.0 mg/mL组细胞抑制率为(27.73±3.75)%,显著高于红花多糖0.5 mg/m L组(P0.05);与对照组比较,红花多糖能够显著提高MDA-MB-435细胞凋亡率(P0.01),且呈剂量依赖性。RT-PCR及Western blotting实验结果显示,与对照组比较,红花多糖能够使MDA-MB-435细胞中PI3K、Akt、mTOR mRNA和蛋白表达显著降低(P0.05、0.01)。结论红花多糖能有效抑制MDA-MB-435细胞的生长,促进其凋亡,作用可能是通过对PI3K/Akt/mTOR通路的阻断实现的。     

基于PI3K/AKT通路研究升降通癃方对前列腺增生细胞的影响

目的:研究升降通癃方通过调节磷脂酰肌醇3-激酶(PI3K)/丝氧酸-苏氨酸蛋白激酶(AKT)信号通路对前列腺增生细胞增殖和凋亡的影响。方法:培养人前列腺增生细胞(BPH-1),随机分为对照组、升降通癃方低、中、高浓度组、阳性组五组,分别给予各组需要的药物处理24 h后,通过四唑盐比色法(CCK8法)检测药物对BPH-1细胞增殖的影响;用细胞划痕实验测定BPH-1的水平迁移能力;通过流式细胞术(FCM)检测升降通癃方对BPH-1细胞细胞凋亡的影响;通过蛋白质印迹法(Western blot)检测药物对细胞中半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、Bcl-2关联X蛋白(Bax)、B淋巴细胞瘤-2(Bcl-2)、磷脂酰肌醇3-激酶(PI3K)、丝氧酸-苏氨酸蛋白激酶(AKT)、重组人α晶状体球蛋白B(Cryab)蛋白表达的影响。结果:加入升降通癃方后,BPH-1的迁移能力明显受到抑制,升降通癃方高、中、低浓度组比较差异有统计学意义(均P<0.05);FCM检测结果显示,升降通癃方组低、中、高浓度组的细胞凋亡率明显高于对照组,差异具有统计学意义(均P<0.05)。Weste...     

黄连活性成分药根碱干预T790M突变EGFR-TKIs耐药非小细胞肺癌的机制研究＊基于网络药理学及实验验证

目的 通过网络药理学及分子对接技术预测黄连活性成分药根碱（Jatrorrhizine）干预表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors，EGFR-TKIs）耐药非小细胞肺癌（non-small cell lung cancer，NSCLC）的效果及作用机制，运用体外细胞学实验进行验证。方法 通过Swiss Target Prediction数据库、PharmMapper数据库、TCMSP数据库及PubMed数据库获得黄连活性成分药根碱的潜在靶标，使用OMIM、Gene Cards及DisGeNET数据库收集非小细胞肺癌相关基因，经人工检查剔除假阳性基因后通过Venn工具获取药根碱和非小细胞肺癌的交集基因，通过PubMed数据库进一步验证靶标后导入STRING数据库，构建蛋白-蛋白相互作用（protein-protein interaction，PPI）网络，通过Cytoscape软件进行拓扑分析，通过DAVID数据库进行GO富集分析及KEGG通路分析，通过KEGG PATHWAY数据库比对药根碱靶标与EGFR-TKIs耐药通路之间的关系，预测药根碱干预EGFR-TKIs耐药非小细胞肺癌的直接作用靶标及靶通路。借助Auto Dock软件进行分子对接验证，PyMol软件进行可视化。采用EGFR-TKIs耐药非小细胞肺癌细胞模型H1975细胞系（即T790M突变EGFR-TKIs耐药非小细胞肺癌细胞系）进行细胞学实验，通过CCK-8初步考察药根碱对H1975细胞增殖能力的影响，采用蛋白质印迹法（Western blot，WB）验证药根碱对H1975细胞中部分关键靶蛋白的调控作用。结果 共获得药根碱靶标328个，非小细胞肺癌疾病基因3965个，药根碱与疾病交集基因69个，有7个核心靶基因为EGFR-TKIs耐药通路相关基因，富集分析显示PI3K-Akt信号通路为重要靶通路，分子对接结果表明药根碱与PI3K及mTOR之间均有较好的结合活性。药根碱可下调靶蛋白PI3K和mTOR的磷酸化，促进H1975细胞凋亡（P<0.01）。结论 黄连活性成分药根碱可能通过PI3K-Akt信号通路发挥抗T790M突变EGFR-TKIs耐药非小细胞肺癌的效用。     

化瘀消癥复方对PI3 K/Akt/mTOR信号通路及输卵管妊娠滋养细胞的作用机制研究

目的探讨化瘀消癥复方对输卵管妊娠滋养细胞的凋亡、侵袭影响及PI3K/Akt/mTOR信号通路的调控机制。方法以不同浓度的化瘀消癥复方水提液干预输卵管妊娠滋养细胞,设立空白组、甲氨蝶呤作为西药组、胞磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)抑制剂LY294002与雷帕霉素靶蛋白(mammalian taget of rapamycin,mTOR)抑制剂雷帕霉素作为对照组,采用流式细胞术检测干预72小时后的细胞凋亡率,采用Transwell法检测细胞侵袭能力,采用蛋白免疫印迹法检测PI3K/Akt/mTOR信号通路蛋白的表达情况。结果各给药组均能上调细胞凋亡率,随着中药浓度的增加,细胞凋亡率上升,中药高剂量组较西药组对凋亡的促进作用更加明显(P<0.05);各给药组均能下调细胞过膜数,随着中药浓度的增加,穿过Transwell侵袭小室的细胞数减少,侵袭减弱,中药高剂量组与西药组对细胞侵袭力影响的对比,差异无统计学意义(P>0.05);中药各组细胞中的p-Akt、p-mTOR蛋白的表达水平随着浓度增加而降低(P<0.05),与上下游通路抑制剂对比,差异无统计学意义(P>0.05)。结论化瘀消癥复方能够促进输卵管妊娠滋养细胞凋亡,抑制侵袭,且呈浓度依赖性,可能与其负调控细胞中PI3K/Akt/mTOR信号通路的活性有关。     

血管软化丸调控PI3K/Akt/mTOR通路影响细胞自噬及抗动脉粥样硬化的作用机制研究

目的通过观察血管软化丸对磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的调控,研究血管软化丸抗动脉粥样硬化的作用机制。方法动物实验,观察各组小鼠主动脉横截面病理损伤程度,观察血管软化丸对小鼠主动脉组织Akt、mTOR mRNA和蛋白质表达。体外实验,观察血管软化丸含药血清、Akt抑制剂康士得、mTOR抑制剂雷帕霉素及mTOR-siRNA对小鼠RAW264.7巨噬细胞的影响,观察巨噬细胞自噬体的变化,观察含药血清对巨噬细胞微管相关蛋白LC3-II表达的影响,观察含药血清对巨噬细胞Akt、mTOR、微管相关蛋白LC3-II及自噬相关蛋白Beclin 1的表达的影响,观察含药血清对巨噬细胞分泌炎症因子水平的影响。结果动物实验显示:血管软化丸组动脉粥样硬化病变程度明显较轻。与对照组比较,血管软化丸组小鼠主动脉组织Akt和mTOR表达水平明显较低(均P<0.05)。体外实验发现,与对照组相比,血管软化丸含药血清组和各抑制剂组透射电镜下观察到自噬体数量明显较大(均P<0.05),巨噬细胞微管相关蛋白LC3-II和Beclin1表达明显升高(均P<0.05),而Akt及mTOR的mRNA及蛋白表达水平明显较低(均P<0.05),巨噬细胞分泌的炎症因子IL-10水平明显高低(P<0.05),而炎症因子IFN-γ水平明显较高(P<0.05)。结论血管软化丸通过抑制炎症反应治疗动脉粥样硬化的分子机制可能与调控PI3K/Akt/mTOR信号通路,调节巨噬细胞自噬,减少斑块巨噬细胞浸润有关。     

补肾活血法调控PI3K/AKT/mTOR通路修复卵巢颗粒细胞自噬损伤机制研究

目的:观察补肾活血法调控磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/AKT/mTOR)通路对体外培养大鼠卵巢颗粒细胞(OGCs)自噬损伤的影响。方法:将原代培养的大鼠卵巢颗粒细胞分为六组：空白对照组、模型组、中药低剂量组、中药中剂量组、中药高剂量组、果纳芬组。采用ELISA法检测各组中雌二醇(E₂)、孕酮(P)分泌量;Western blot法和免疫荧光法分别检测各组OGCs中PI3K、AKT、mTOR及自噬关键分子酵母Atg6同系物1(Beclin 1)、微管相关蛋1轻链3(LC3)、自噬受体蛋白p62的蛋白表达。结果:模型组E₂含量显著降低,中药各剂量组E₂含量均上升(均P<0.05),且中药高剂量组与果纳芬组E₂含量相当;各组对P的含量均没有影响(均P>0.05)。中药各剂量组及果纳芬组p-PI3K、p-AKT、p-mTOR水平和p62的表达上调,Beclin 1和LC3Ⅱ/LC3Ⅰ的表达下调,且中药高剂量组效果优于果纳芬组(均P<0.05)。结论:补肾...     

老鼠簕生物碱A对肝纤维化大鼠PI3K/Akt/m TOR/p70S6K信号通路的影响

目的观察老鼠簕生物碱A(HBOA)对四氯化碳(CCl4)致肝纤维化大鼠磷酸肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(m TOR)/p70核糖体蛋白S6激酶(p70S6K)信号通路的影响,探讨HBOA抗肝纤维化的作用机制。方法大鼠随机分成对照组、模型组及HBOA高、中、低剂量(100、50、25 mg/kg)组和秋水仙碱(0.4 mg/kg)组。除对照组外,其余各组ig给予50%CCl4橄榄油溶液,每周2次,连续12周,诱导肝纤维化大鼠模型。于造模第9周起,给药组分别ig相应的受试药物,每天1次,给药4周。实验结束后,计算各组大鼠体质量变化、肝脏指数;检测各组大鼠肝匀浆中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性;蛋白免疫印迹法(Western blotting)法检测肝组织P-PI3K、p-Akt、p-mTOR、p-p70S6K蛋白的表达。结果与模型组比较,各给药组大鼠体质量增加量显著升高,均能降低肝脏指数及肝组织中ALT、AST活性;此外,HBOA高、中剂量组均能显著抑制p-PI3K、p-Akt、p-m TOR、p-p70S6K蛋白的表达。结论 HBOA对肝纤维化大鼠具有一定的保护作用,其机制可能与抑制PI3K/Akt/m TOR/p70S6K信号通路有关。     

中药抑制非小细胞肺癌PI3K/Akt/mTOR信号通路克服EGFR-TKIs获得性耐药研究进展

随着对肺癌发病机制及其生物学特性研究的不断深入,分子靶向治疗尤其是表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKIs)在非小细胞肺癌治疗方面取得了突破性进展,然而经过6~12个月的治疗后,大部分患者会对EGFR-TKIs产生获得性耐药。PI3K/Akt/mTOR信号通路在非小细胞肺癌的发生发展中具有重要的作用,该通路在肿瘤治疗方面已经有了比较广泛的研究。中药在对抗EGFR-TKIs耐药方面有很大的前景。就近年来中药通过抑制非小细胞肺癌PI3K/Akt/mTOR信号通路来克服EGFR-TKIs获得性耐药的研究进展进行综述。     

基于mTOR/p70S6K信号通路探讨中医药治疗甲状腺恶性肿瘤作用机制进展

哺乳动物雷帕霉素靶蛋白(mTOR)是高度保守的丝/苏氨酸蛋白激酶,可感知并整合多种生物信号,调节细胞的生长、凋亡、自噬,参与免疫抑制以及细胞迁移,其过度表达为肿瘤细胞的生长和转移提供了物质基础和动力.mTOR/p70S6K信号传导的异常表达可以影响甲状腺细胞的生长代谢,调节甲状腺癌细胞的生长和转移.现针对mTOR信号通...     

PI3K/Akt信号通路影响食管癌细胞生长的机制及中药干预作用研究进展

食管癌是我国肿瘤发病死亡率较高的恶性肿瘤之一,国家癌症中心2019年发布的中国最新癌症报告中显示,2015年食管癌患病人口达到了24. 6万人,死亡人数高达18. 8万人。如何有效的治疗食管癌,提高患者的生存率也是当今医学领域中亟待解决的首要问题之一。磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路是调节机体内细胞存活、分化及凋亡的重要信号通路之一,在各种癌症的发生及作用机制中起到了重要的作用。近年来的研究表明,PI3K/Akt信号通路的激活是调节食管癌细胞的增殖、凋亡、周期阻滞、迁移与侵袭的重要因素。长期的临床观察发现中药治疗食管癌作用平稳、毒副作用小,尤其在改善肿瘤患者的生活质量,延长患者生存期等方面作用独特、效果显著。用中药干预该信号通路以探索其对食管癌的作用机制是目前中药治疗食管癌的研究热点。本文对2009—2019年CNKI,Pubmed数据库中PI3K/Akt信号通路,食管癌,miRNA为关键词进行检索,共检索文献226篇,整理、归纳与中药,食管癌,miRNA,PI3K/Akt信号通路相关文献61篇。综述了PI3K/Akt信号通路在食管癌中的作用机制,miRNA与PI3K/Akt信号通路与食管癌发生发展的关系以及中药如何通过调控PI3K/Akt信号通路中相关蛋白的表达而抑制细胞增殖、影响细胞生长周期、诱导细胞凋亡、诱导细胞自噬、抑制肿瘤的侵袭和转移、抑制血管生成等,最终对食管癌起到一定的改善作用。对中医药治疗食管癌提供理论基础以及科学依据。     

中医药干预相关信号通路防治肝癌研究进展

肝癌的发生、发展及微环境中存在着多种信号通路的异常。细胞信号通路的异常持续激活或抑制,调控细胞的增殖、凋亡及迁移,进而影响炎症、血管生成和肿瘤迁移。中医药可通过干预相关信号通路的转导发挥防治肝癌的作用,主要包括刺猬信号通路、IL-6/STAT3信号通路、NF-κB信号通路、PI3K/Akt/mTOR信号通路、MAPK信号通路、TLR信号通路、Wnt信号通路等。现阶段中医药防治肝癌作用确切,但具体机制尚未完全阐明,中医药调控肝癌相关信号通路的研究仍需继续探索。     

中药抗肿瘤血管生成的信号通路研究

血管生成是肿瘤发生和转移的基本条件。调控肿瘤血管生成相关的信号通路包括PI3K/Akt/mTOR、Ras/Raf/MEK/ERK、Notch转导通路等。中药抗肿瘤血管生成的信号通路研究越来越受关注。调控PI3K/Akt/mTOR通路的中药多集中于抑制Akt的磷酸化,且清热药居多。调控Ras/Raf/MEK/ERK通路的中药多集中于抑制ERK的磷酸化,且活血化瘀药居多。调控Notch转导通路的中药多集中于抑制Notch1的表达,对配体的表达不一。对中药抗肿瘤血管生成的信号通路进行综述,旨在寻求新的血管生成抑制剂,阐明作用靶点,为肿瘤研究提供方向。     

[6]‐Gingerol enhances the cisplatin sensitivity of gastric cancer cells through inhibition of proliferation and invasion via PI3K/AKT signaling pathway

Cisplatin‐based chemotherapy is a widely used chemotherapeutic regimen for gastric cancer; however, drug resistance limits its efficacy. [6]‐Gingerol has been found to exhibit anticancer effects. Here, we aim to explore the potential of [6]‐gingerol in combination with cisplatin as a new regimen for gastric cancer. CCK‐8 assay and colony formation assay were used to determine the effect of [6]‐gingerol in combination with cisplatin on cell viability of gastric cancer cells. Flow cytometry was performed to assess cell cycle distribution. Wound‐healing assay and transwell invasion assay were conducted to examine the migration and invasion abilities. Cell cycle and invasion‐related proteins and mRNAs, as well as PI3K/AKT signaling proteins, were assessed by western blotting and quantitative real‐time polymerase chain reaction. Combination of [6]‐gingerol with cisplatin inhibited cell viability and enhanced cell cycle arrest at G1 phase compared with cisplatin alone. The combination treatment inhibited cell migration and invasion ability and decreased cyclin D1, cyclin A2, matrix metalloproteinase‐9, p‐PI3K, AKT, and p‐AKT protein expressions and increased P21 and P27 mRNA levels. Our study demonstrates that [6]‐gingerol enhances the cisplatin sensitivity of gastric cancer cells and that the mechanisms involve G1 phase arrest, migration and invasion suppression via PI3K/AKT signaling pathway.