PTEN/PI3K/Akt信号通路对K562细胞凋亡调控的研究

 目的 探讨PTEN/PI3K/Akt信号传导通路对人慢性粒细胞白血病细胞系K562的增殖、凋亡调控的研究及可能的分子作用机制。 方法 将携带有野生型PTEN及绿色荧光蛋白的腺病毒（Ad-PTEN-GFP）及空载体（Ad-GFP）腺病毒,转染人慢性粒细胞白血病细胞系K562。通过MTT检测细胞生长曲线,流式细胞术检测细胞凋亡率和细胞增殖指数,同时用细胞光镜、电镜形态等方法检测细胞凋亡,荧光定量PCR（FQ-PCR）检测PTEN及凋亡相关基因Bcl-2、Bcl-_xL、Bax mRNA水平变化,Western blot检测PTEN及Akt、p-Akt蛋白水平变化。 结果 与Ad-GFP组相比,Ad-PTEN-GFP 转染K562细胞后,细胞增殖受抑,增殖指数降低,凋亡率增加,p-Akt表达降低,抗凋亡相关基因Bcl-2、Bcl-_xL mRNA表达降低,促凋亡基因Bax mRNA表达增加。 结论 过表达PTEN可能通过抑制PI3K/Akt通路抑制K562细胞系增殖,促进细胞凋亡。     

芹菜素通过 PI3K/Akt 信号通路诱导 Hela 细胞凋亡

目的：初探芹菜素（Apigenin）对人宫颈癌细胞 Hela 的抑制机制。方法：MTT 法检测 Apigenin 对 Hela细胞的增殖抑制作用,实时无标记细胞分析技术测量 Apigenin 对 Hela 细胞生长曲线的影响。Western blot 检测 Apigenin 对 Hela 细胞中 PI3K/ Akt 信号通路的影响。结果：与阴性对照组相比,Apigenin 能显著抑制 Hela细胞的增殖（P <0.01）,当药物浓度为20μmol/ L 时抑制率达到（80.5±5.3）%,IC50值为（6.8±0.8）μmol/ L。细胞生长曲线反映,Apigenin 减缓了 Hela 细胞的增殖,对数期细胞经20μmol/ L Apigenin 处理后,细胞数量迅速下降。Western blot 结果显示,Apigenin 能显著抵抗 IGF -1引起的 Akt 激活但并不能降低 PI3K 的磷酸化水平。同时 Apigenin 还能降低 Bcl -2/ Bax 比例,提高 Caspase -3活性,启动细胞线粒体凋亡。结论：Apigenin可以通过 PI3K/ Akt 信号通路促进 Hela 细胞的凋亡。     

PI3K/Akt信号通路在肿瘤化疗耐药中的作用

磷脂酰肌醇3-激酶-蛋白激酶B(PI3K/Akt)信号通路在细胞内发挥重要的作用,参与了许多生理和病理活动.目前研究发现在许多肿瘤中过度激活的PI3K/Akt信号通路与肿瘤化疗耐药的产生密切相关,体外研究显示采用PI3K/Akt信号通路抑制剂可以逆转肿瘤细胞的耐药.本文简要介绍了PI3K/Akt信号通路的基本组成结构,并重点介绍其在肿瘤化疗耐药中的作用.     

PI3K—Akt信号通路与胃癌的研究进展

细胞内信号传导通路PI3K—Akt与胃癌的发生、生长及化疗耐药关系密切。本文概述了PI3K—Akt的分类结构、PI3K—Akt信号转导通路的调节、与胃癌细胞凋亡及血管生成的关系及化疗耐药和放疗的机制。     

PI3K/Akt/mTOR信号转导通路与非小细胞肺癌

肺癌是目前世界上发病率和死亡率最高的恶性肿瘤之一,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)占肺癌的75%-85%,确诊时多属中晚期,常规放、化疗效果欠佳,5年生存率仅为5%-10%.PI3K/Akt/mTOR信号通路作为细胞内重要信号转导通路之一,通过影响下游多种效应分子的活化状态,与NSCLC的发生发展密切相关.本文综述了PI3K/Akt/mTOR信号通路的组成,其抑制凋亡、促进增殖的关键作用以及在NSCLC中的研究现状,以期为NSCLC的治疗寻找潜在的靶点.     

大鼠乳腺癌骨转移模型中PI3K/Akt信号通路参与诱导疼痛

目的 探讨骨癌痛大鼠模型中PI3K/Akt信号通路参与痛觉过敏的产生和维持及其脊髓机制.方法 Wistar大鼠,体重在180~200 g,将大鼠随机分为3组:癌痛模型组(A组)、假手术组(B组)、正常组(C组),A组大鼠左侧胫骨髓腔内单次注入Walker256乳腺癌细胞建立大鼠胫骨癌痛模型,B组大鼠左侧胫骨注入等量生理盐水,C组做不给药处理.A组造模后第7天,评估筛选成模的大鼠,随机分为3组:癌痛组(A1组)、癌痛+NS组(A2组)、癌痛+抑制剂组(A3组).正常对照组(C组)随机分为2组:空白对照组(C1组)、空白+抑制剂组(C2).A3组和C2组分别在第13、14、21天鞘内注射Akt抑制剂GSK690693,A2组在第13、14、21天鞘内注射等量生理盐水,A1组、B组、C1组均不给药处理.在第0、7、14、21天,分别检测大鼠机械性缩足阈值(mechanical withdrawal threshold,MWT)和热缩腿潜伏期(thermal withdrawal latency,MWT).第21天行为学测试后处死大鼠,取大鼠脊髓L4~L6区段,用免疫组化及Western blot检测大鼠脊髓的磷酸化Akt(p-Akt)水平.结果 实验观察到大鼠的MWT和TWL均显著降低,第7天及14天A1组、A2组、A3组及B组分别与C1组比较,P<0.05,第21天A3组与A1组、A2组分别比较,P<0.05.与C1组比较,骨癌痛模型组大鼠脊髓背角p-Akt表达增强,鞘内注射Akt抑制剂可降低脊髓背角p-Akt的表达.结论 PI3K/Akt信号通路参与了骨癌痛的中枢敏化,在大鼠骨癌痛发生发展过程中起着重要作用.     

PI3K/Akt信号通路与肿瘤血管新生的研究进展

PI3K/Akt信号通路在多种细胞中活化,参与细胞的增殖、分化、凋亡、血管新生等病理、生理过程。血管的生成需要PI3K/Akt信号通路的激活,PI3K/Akt活化后可以广泛诱导鸡胚尿囊膜血管的生成。PI3K/Akt信号通路与其下游信号分子mTOR及多种促血管新生因子,如VEGF、HIF等相互作用,从而促进肿瘤血管新生。PI3K/Akt信号通路抑制剂能够抑制其血管新生作用,因此靶向PI3K/Akt信号通路为恶性肿瘤靶向治疗提供了新方法。     

苦参碱对视网膜母细胞瘤细胞增殖、凋亡及PI3K/Akt信号通路的影响

目的 探讨苦参碱（Mat）对视网膜母细胞瘤细胞Y79细胞增殖、凋亡及PI3K/Akt信号通路的影响。方法 Y79细胞经0.5、1.0、1.5 g/L Mat处理24 h后,采用CCK-8试剂盒检测细胞增殖情况,磷酯酰丝氨酸结合蛋白-异硫氢酸荧光素/碘化丙啶（Annexin V-FITC/PI）双标记流式细胞术检测细胞凋亡情况,Western blotting免疫印迹检测各浓度Mat处理后凋亡相关蛋白Bcl-2及Bax、PI3K/Akt信号通路重要蛋白PI3K p85亚基、Akt及其磷酸化形式p-Akt的蛋白水平。结果 不同浓度Mat作用Y79细胞24 h后,可呈浓度依赖性方式抑制细胞增殖,增加细胞凋亡率（P＜0.05）。Western blotting检测发现,Mat可明显增加促凋亡蛋白Bax表达,降低抗凋亡蛋白Bcl-2水平并可降低PI3K p85α亚基及磷酸化Akt的蛋白水平（P＜0.05）,对总Akt水平无明显影响。结论 Mat可抑制人视网膜母细胞瘤增殖并诱导其凋亡,可能与抑制PI3K/Akt 信号通路有关。     

红花多糖抑制PI3K/Akt信号通路诱导人胃癌细胞凋亡的研究

目的 探讨红花多糖通过抑制PI3K/Akt信号通路调控胃癌细胞凋亡的机制。方法 MTT比色法观察SPS对人胃癌SGC-7901细胞体外增殖的抑制作用,流式细胞仪(FCM)分析细胞凋亡,实时荧光定量RT-PCR法和Western Blot法检测蛋白激酶B(Akt)基因及蛋白的表达情况。结果 红花多糖在一定范围内以剂量依赖方式和时间依赖方式抑制SGC-7901胃癌细胞生长。流式细胞仪检测,SGC-7901细胞经红花多糖处理24 h,其早期凋亡率、细胞坏死或晚期凋亡率显著增加,呈现明显的剂量依赖性。Real-time PCR和Western Blot检测发现,SPS处理的细胞Akt基因及蛋白表达量明显下降。结论 红花多糖对人胃癌SGC-7901细胞体外增殖具有明显的抑制作用,该抑制作用具有一定的时间依赖性和剂量依赖性;红花多糖能够下调Akt mRNA表达,降低Akt和p-Akt蛋白的表达量,抑制Akt通路发挥抗肿瘤作用。     

PI3K/Akt/mTOR信号通路在三阴性乳腺癌治疗中的研究进展

摘 要：三阴性乳腺癌是乳腺癌中的一种特殊分型,异质性强,有效作用靶点不明,具有侵袭早,转移快,预后差等特点,5年生存率低,是乳腺癌中病死率最高的一种亚型。目前已对一些潜在的分子靶点做了一些实验,但一些研究发现,PI3K/Akt/mTOR信号通路抑制剂对于三阴性乳腺癌的抑制作用更为明显,一些抑制剂已经进入了预试验或早期临床试验阶段。该文主要介绍三阴性乳腺癌的分子分型,PI3K/Akt/mTOR信号传导通路的异常激活机制及所涉及的关键基因在三阴性乳腺癌中的表达水平和相关抑制剂的治疗加以综述,以期为该类型的乳腺癌提供更好的治疗途径。     

Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway.

The PTEN protein is a lipid phosphatase with putative tumor suppressing abilities, including inhibition of the PI3K/Akt signaling pathway. Inactivating mutations or deletions of the PTEN gene, which result in hyper-activation of the PI3K/Akt signaling pathway, are increasingly being reported in human malignancies, including breast cancer, and have been related to features of poor prognosis and resistance to chemotherapy and hormone therapy. Prior studies in different tumor models have shown that, under conditions of PTEN deficiency, the PI3K/Akt signaling pathway becomes a fundamental proliferative and survival pathway, and that pharmacological inhibition of this pathway results in tumor growth inhibition. This study aimed to explore further this hypothesis in breast cancer cells. To this end, we have determined the growth response to inhibition of the PI3K/Akt signaling pathway in a series of breast cancer cell lines with different PTEN levels. The PTEN-negative cell line displayed greater sensitivity to the growth inhibitory effects of the PI3K inhibitor, LY294002 and rapamycin, an inhibitor of the PI3K/Akt downstream mediator mTOR, compared with the PTEN-positive cell lines. To determine whether or not these differences in response are specifically due to effects of PTEN, we developed a series of cell lines with reduced PTEN protein expression compared with the parental cell line. These reduced PTEN cells demonstrated an increased sensitivity to the anti-proliferative effects induced by LY294002 and rapamycin compared with the parental cells, which corresponded to alterations in cell cycle response. These findings indicate that inhibitors of mTOR, some of which are already in clinical development (CCI-779, an ester of rapamycin), have the potential to be effective in the treatment of breast cancer patients with PTEN-negative tumors and should be evaluated in this setting.     

骨唾液酸蛋白对乳腺癌 MDA-MB-231 细胞 PI3K-AKT 信号通路的影响

目的:探讨骨唾液酸蛋白(bone sialoprotein,BSP)对乳腺癌MDA-MB-231细胞PI3K-AKT信号通路的影响。方法:BSP基因沉默的乳腺癌MDA-MB-231细胞(简称231BO-BSP27)经重组人BSP(recombinant human BSP,rhBSP)和PI3K-AKT抑制剂LY294002处理后,Western blotting检测磷酸化AKT水平的变化,实时定量PCR检测caspase-3、cyclin D1 mRNA表达水平,MTT法检测细胞增殖能力。结果:与BSP基因未沉默的对照组231BO-Scrambled细胞相比,BSP基因沉默的231BO-BSP27细胞BSP蛋白表达明显下调(74.32±2.18)%(P<0.01);AKT磷酸化水平明显下降(33.30±2.61)%(P<0.01),而caspase-3和cyclin D1 mRNA表达分别上升和下降(1.000±0.000 vs 1.733±0.039,1.000±0.000 vs 0.370±0.012;均P<0.01);231BO-BSP27细胞增殖能力显著下降(P<0.05)。外源添加rhBSP蛋白分别上调231BO-Scrambled和231BO-BSP27细胞AKT磷酸化水平(17.86±2.27)%和(33.78±1.51)%(均P<0.01),231BO-BSP27细胞caspase-3 mRNA表达降低(1.000±0.039 vs 0.541±0.091,P<0.01)、cyclin D1 mRNA表达升高(1.000±0.000 vs 2.921±0.032,P<0.01),促进231BO-Scrambled和231BO-BSP27细胞的增殖(均P<0.01)。LY294002则能逆转rhBSP对231BO-Scrambled和231BO-BSP27细胞AKT磷酸化激活作用(P<0.05),使231BO-BSP27细胞caspase-3 mRNA表达升高(P<0.01)、cyclin D1 mRNA表达降低(P<0.01),使该两种细胞增殖能力下降(均P<0.01)。结论:BSP通过PI3K-AKT信号通路调控乳腺癌MDA-MB-231细胞caspase-3和cyclin D1的表达,并影响细胞的增殖。     

PI3K-Akt信号通路阻断在乳腺癌治疗中的作用

分子靶向药物为肿瘤的治疗提供了新的方向。抑制信号通路中一些小分子的活性,从而阻断某些信号的转导,成为肿瘤治疗中的新的策略。在肿瘤的发生、发展过程中,经常伴有P13K信号通路的异常改变。过度激活P13K-Akt信号通路之后,可以引起一系列的反应,包括细胞的生长、增殖和转移,上皮细胞向间叶细胞的转变以及血管的生成。因此,这条信号通路成为人们比较感兴趣的分子治疗的靶标。另外,在一些实验中,过度表达P13K或者Akt,特别是当它们持续活化时,就足以引起细胞的恶性转变,并且能够使细胞产生耐药。当P13K-Akt信号通路被阻断之后,具有高水平Akt的细胞生长就会受到抑制,并且开始凋亡。由于某些肿瘤细胞的存活和生长对P13K-Akt信号通路的依赖,使分子靶向药物能够比较特异的杀死肿瘤细胞。在过去的几年中,人们已经找到了一些此信号通路的抑制剂。我们介绍了P13K-Akt信号通路以及阻断此信号通路在乳腺癌治疗中的应用,重点介绍pAkt和mTOR的分子抑制剂。     

Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion

Activated phosphoinositide 3-kinase (PI3K) and its downstream target Akt/PKB are important signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis and oncogenesis. We investigated the role of the PI3K-Akt signaling pathway in the invasion of prostate cancer cell lines and activation of this pathway in primary human prostate tumors. Treatment of human prostate cancer cells viz. LNCaP, PC-3 and DU145 with PI3K pharmacological inhibitor, LY294002, potentially suppressed the invasive properties in each of these cell lines. Restoration of the PTEN gene to highly invasive prostate cancer PC-3 cells or expression of a dominant negative version of the PI3K target, Akt also significantly inhibited invasion and downregulated protein expression of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9, markers for cell invasion, indicating a central role of the PI3K-Akt pathway in this process. Immunoblot analysis of PI3K and total/activated levels of Akt showed increased protein levels of catalytic (p110alpha/beta) and regulatory (p85) subunits of PI3K and constitutive Akt activation in high-grade tumors compared to low-grade tumor and benign tissue. Immunohistochemical analyses further confirmed a progressive increase in p-Akt (p-Ser473) levels but not of total-Akt (Akt1/2) in cancer tissues compared to benign specimens. A successive increase in p-Akt expression was further noted in specimens serially obtained from individuals with time-course disease progression. Taken together, these results suggest that aberrant activation of PI3K-Akt pathway may contribute to increased cell invasiveness and facilitate prostate cancer progression.     

Activation of IL-8 via PI3K/Akt-dependent pathway is involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells

Background Information: Previous studies have revealed that leptin may be involved in epithelial-mesenchymal transition (EMT), a crucial initiator of cancer progression to facilitate metastatic cascade, increase tumor recurrence, and ultimately cause poor prognosis. However, the underlying mechanism remains unclear. The aim of our present study was to investigate the effect of leptin on EMT of breast cancer cells and the underlying mechanism. Results: Our data demonstrated that leptin significantly increased the phosphorylation of STAT3, Akt, and ERK1/2, elevated the expression of IL-8, and induced breast cancer cells to undergo EMT. The effect of leptin on IL-8 could visibly abolished by the inhibitor of PI3K {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002. In addition, leptin-induced EMT of breast cancer cells was blocked by anti-IL-8 antibodies. Examination of the expression of ObR, leptin, IL-8 and EMT-related biomarkers in patient specimens demonstrated that malignant breast carcinoma with lymph node metastases (LNM), which represents poor prognosis, expressed higher levels of ObR, leptin, IL-8 than other types of breast cancer, and displayed more obvious EMT transversion. In vivo xenograft experiment revealed that leptin signally promoted tumor growth and metastasis and increased the expressions of IL-8 and EMT-related biomarkers. Conclusions: Our results support that leptin-induced EMT in breast cancer cells requires IL-8 activation via the PI3K/Akt signal pathway.     

PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations

The activation of the PI3K signaling pathway resulting from genetic alterations induces carcinogenesis and resistance to anticancer therapies. Breast cancer is a major malignancy that is associated with dysregulation of the PI3K signaling pathway. PIK3CA mutations and PTEN loss occur in every subtype of breast cancer. PI3K inhibitors are being evaluated in breast cancer after the success of an alpha isoform-specific PI3K inhibitor in estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer. Some preclinical data indicate the potential for PI3K/mTOR targeting in combination with trastuzumab for HER2-positive breast cancer with or without expression of the estrogen receptor. However, the role of this therapy in HER2-positive breast cancer with PIK3CA mutations and/or PTEN loss remains unclear. We examined three HER2-positive, ER-negative breast cancer cell lines to determine the efficacy of a novel alpha isoform-specific PI3K inhibitor in combination with trastuzumab. The results indicated that this combination was effective in PIK3CA-mutant or PTEN-deficient breast cancer cells by inducing apoptosis and inhibiting the expression of downstream proteins. PTEN loss by siRNA modulation in parental HER2-positive cancer cells with PI3K signaling pathway alterations could not confer resistance to alpelisib or GDC-0077 plus trastuzumab. We selected the CK-MB-1 cell line without alterations in the PI3K pathway to demonstrate that PI3K inhibitors plus trastuzumab represented a biomarker-specific treatment. In vivo effects of alpelisib plus trastuzumab were tested and confirmed in a mouse model, showing the combination strategy offered the best opportunity to achieve tumor volume reduction. With known safety profiles, this cytotoxic chemotherapy-free regimen warrants further attention as a biomarker-driven strategy for treating HER2-positive breast cancer.     

PI3K/Akt信号通路在RANKL诱导的MCF-7乳腺癌细胞迁移中的作用

目的：核因子-κB受体活化因子配体（RANKL）能促进表达RANK的上皮癌细胞迁移至骨,与乳腺癌骨转移密切相关。本文探讨磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶（phosphoinositide3-kinase/serine/threonine protein kinase PI3K/Akt）信号通路在RANKL诱导的乳腺癌MCF-7细胞迁移中的作用。方法：流式细胞仪检测MCF-7细胞表面RANK蛋白的表达;Transwell法测定RANKL刺激后MCF-7细胞迁移能力的改变;Western-blot检测MCF-7细胞RANKL刺激后p-Akt及Akt的表达。SPSS 16.0软件分析实验数据。结果：MCF-7细胞表达RANK蛋白,RANKL诱导MCF-7细胞迁移能力显著增强,RANKL的圈套受体OPG可阻断RANKL诱导的细胞迁移。RANKL刺激后MCF-7细胞p-Akt表达在1、5分钟时一过性升高,PI3K抑制剂LY294002显著抑制RANKL诱导的细胞迁移。结论：PI3K/Akt信号通路参与RANKL诱导的乳腺癌细胞系MCF-7迁移。     

PI3K/Akt信号通路在RANKL诱导的MCF-7乳腺癌细胞迁移中的作用

目的 核因子-κB受体活化因子配体(RANKL)能促进表达RANK的上皮癌细胞迁移至骨,与乳腺癌骨转移密切相关.本文探讨磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶(phosphoinositide3-kinase/serine/threonine protein kinase PI3K/Akt)信号通路在RANKL诱导的乳腺癌MCF-7细胞迁移中的作用.方法 流式细胞仪检测MCF-7细胞表面RANK蛋白的表达;Transwell法测定RANKL刺激后MCF-7细胞迁移能力的改变;Western-blot检测MCF-7细胞RANKL刺激后p-Akt及Akt的表达.SPSS 16.0软件分析实验数据.结果 MCF-7细胞表达RANK 蛋白,RANKL诱导MCF-7细胞迁移能力显著增强,RANKL的圈套受体OPG可阻断RANKL诱导的细胞迁移.RANKL刺激后MCF-7细胞p-Akt表达在1、5分钟时一过性升高,PI3K抑制剂LY294002显著抑制RANKL诱导的细胞迁移.结论 PI3K/Akt信号通路参与RANKL诱导的乳腺癌细胞系MCF-7迁移.     

PI3K/Akt途径在朊蛋白介导胃癌耐药中的作用研究

目的:探讨PI3K/Akt途径在朊蛋白(PrPc)介导胃癌耐药中的作用.方法:脂质体基因转染法建立高表达PrPc的胃癌细胞亚系.Western印迹检测转染细胞中Akt蛋白的表达.噻唑蓝(MTT) 比色法测定单独或联用PI3K抑制剂LY294002时转染细胞对化疗药物的敏感性.流式细胞仪检测单独或联用LY294002时转染细胞内阿霉素蓄积和潴留.结果:将PrPc正义载体pcDNA-PrP转入SGC7901,成功建立PrPc高表达胃癌细胞亚系并命名为PS;空载体转染细胞命名为BS.Western-Blot显示磷酸化Akt在PS中的表达较BS及SGC7901增高,而三者的总Akt则无差别.未经LY294002处理时,在阿霉素或长春新碱的作用下,PS的存活率分别为91.4%±3.4%和89.4%±3.8%,较BS(79.2%±4.3%和75.9%±2.1%)明显增高(均 ),PS细胞内阿霉素蓄积量和潴留量分别为4.4±0.3和4.2±0.4,明显低于BS(8.2±0.5和8.0±0.3)(均 );当联合LY294002处理后,PS在两种药物作用下的存活率均随着LY294002浓度的增加逐渐降低,并均在LY294002为30μmol/L时接近BS(均 ),PS细胞内阿霉素蓄积量和潴留量逐渐增高,并均在LY294002为30μmol/L时接近BS(均 ).结论:PrPc介导的胃癌耐药与PI3K/ Akt途径活性密切相关,抑制PI3K/ Akt途径活性可逆转PrPc介导的胃癌耐药.     

抑制PI3K/Akt信号转导通路提高化疗效果的实验研究

目的:探讨通过抑制PI3K/Akt信号转导通路提高抗癌药物对恶性肿瘤细胞的杀伤作用。方法:采用噻唑蓝(MTT)比色法检测塞莱昔布、顺铂及多西紫杉醇单独或联合PI3K抑制剂LY294002对人宫颈癌HeLa细胞和人乳腺癌MCF7细胞的抑制率;采用流式细胞技术检测药物单独或联合作用对HeLa细胞和MCF7细胞凋亡的影响。结果:①联合LY294002能够显著提高塞莱昔布、顺铂及多西紫杉醇对HeLa细胞和MCF7细胞抑制率(P<0.05)。②LY294002与塞莱昔布、顺铂及多西紫杉醇的协同治疗指数均小于1,具有协同治疗作用。③联合LY294002能够增加HeLa细胞和MCF7细胞的凋亡水平。结论:抑制PI3K/Akt信号转导通路能够显著提高塞莱昔布、顺铂及多西紫杉醇对HeLa细胞和MCF7细胞的杀伤作用。