人胶质瘤干细胞趋化因子受体CXCR4活化促进血管生成的作用

目的从人恶性胶质瘤细胞系U87中分离、培养和鉴定胶质瘤干细胞,观测其CXCR4表达情况及其活化后促血管生成因子分泌的变化。方法通过流式细胞术检测U87细胞中CD133阳性细胞的比例。使用CD133免疫磁珠分离试剂盒通过磁性细胞分选系统分离胶质瘤干细胞。采用间接免疫荧光标记、激光共聚焦扫描显微术观测胶质瘤干细胞中神经巢蛋白（nestin）、胶质纤维酸性蛋白（GFAP）、趋化因子受体CXCR4的表达;以CXCR4配体刺激通过钙流试验检测受体功能,采用酶联免疫吸附试验（EIJSA）检测培养上清中血管内皮生长因子（VEGF）和白细胞介素-8（IL-8）的含量。建立裸鼠皮下移植瘤模型,观察胶质瘤干细胞成瘤情况及瘤体内VEGF表达情况。结果U87细胞系中CD133阳性细胞的比例为0．5％,这些细胞具有干细胞增殖和生长特性;它们表达CXCR4,用其相应配体激活后导致胞内钙流增加、分泌VEGF和IL-8增多。与CD133阴性细胞相比,CD133阳性细胞在体外分泌VEGF、IL-8多,在体内成瘤率高,形成的移植瘤生长迅速,表达更多VEGF。结论人恶性胶质细胞瘤细胞系U87中含有极少量胶质瘤干细胞,表达功能性CXCR4、分泌更多促血管生成因子,提示这些干细胞也直接参与胶质瘤血管生成。     

胃癌组织中CXCL12和CXCR4的表达及意义

目的观察趋化因子CXCL12及其特异性受体CXCR4在人胃癌组织中的表达,探讨其与临床病理参数、预后的关系。方法选择120例胃癌标本,应用免疫组化SP法检测CXCL12和CXCR4在人胃癌组织中的表达,分析CXCL12和CXCR4的表达与患者临床病理参数、术后生存率之间的关系。结果胃癌组织及正常胃黏膜组织中均可检测到CXCL12、CXCR4的表达,但胃癌组织中的表达水平均明显高于正常胃黏膜组织,表达差异有显著性(P<0.05)。CXCL12阳性与CXCR4阳性呈正相关(r=0.276,P<0.05)。胃癌CXCL12和CXCR4的表达水平与肿瘤细胞淋巴结转移及分化程度密切相关(P<0.05),与患者的年龄、性别、肿瘤的大小、浸润深度及远处转移等无关(P>0.05)。CXCL12和CXCR4阳性表达的患者其五年生存率明显低于其阴性表达的患者。结论胃癌中CXCL12和CXCR4的高表达与胃癌的生物学行为及预后密切相关,检测其表达对预测胃癌的转移及判断预后有一定价值。     

The CXCR4/CXCL12 axis in endometrial cancer

Chemokines and their receptors seem to act as important regulators of the metastatic cascade. CXCL12 and its receptor CXCR4 were shown to be involved in human cancer progression. There is increasing evidences suggesting that the expression of CXCR4 in human cancers is correlated with poor patient prognosis and that CXCR4 neutralization can prevent metastases in vivo. Here we tested the role of the CXCR4/CXCL12 axis in a neoplasia with a reduced risk of metastatic progression, such as human endometrial cancer. CXCR4 and CXCL12 mRNA expression was measured in 41 endometrial cancers and in corresponding not affected tissues. The expression of CXCR4 was predominant in endometrial cancer (P = 0.035) whereas CXCL12 was overexpressed in normal mucosae (P = 0.002). CXCR4 expression (P = 0.035), but not CXCL12, was significantly related to cancer differentiation. Endometrial cancer cells (HEC1A) were able to generate diffuse metastases in peritoneum, lung and liver of CD-1 nude mice, but the simultaneous treatment with a neutralizing anti-CXCR4 monoclonal antibody dramatically reduced the number and the size of metastases in the animals. In conclusion, our data seem to indicate that the CXCR4-CXCL12 axis can play a role in the progression of endometrial carcinoma and that specific therapies with antagonists of chemokines receptors could be of help in the treatment of metastatic patients.     

Roles of Chemokine Receptor 4 （CXCR4） and Chemokine Ligand 12 （CXCL12） in Metastasis of Hepatocellular Carcinoma Cells

Chemokines are involved in human hepatocellular carcinoma （HCC） carcinogenesis. However, the exact mechanism of chemokines in HCC carcinogenesis remains unknown. Here we investigated the roles of chemokine receptor 4 （CXCR4） and chemokine ligand 12 （CXCL12） in the metastasis of HCC. We found that the expression levels of CXCR4 mRNA in HCC tissues, MHCC97 cells, and HUVEC cells were 2.52 ±1.13, 2.34 ±1.16 and 1.63 ±1.26, respectively and that the CXCR4 protein levels were 1.38 ± 0.13, 1.96± 0.32 and 1.86 ±0.21, respectively. In contrast, CXCR4 was not detected in normal hepatic tissues. In 78 HCC patients, we also found that the concentration of CXCL12 in cancerous ascitic fluid was 783-8,364 pg/ml and that CXCL12 mRNA level in HCC metastasis portal lymph nodes was 1.21 ± 0.87 but undetectable in normal hepatic tissues. Finally we discovered that recombinant human CXCL12 could induce MHCC97 cells and HUVEC cells to migrate with chemotactic indexes （CI） of 3.9 ±1.1 and 4.1± 1.6, respectively. Cancerous ascitic fluid could also induce the migration of MHCC97 cells with a CI of 1.9 ± 0.8. Thus, our data suggest that CXCR4 and CXCL12 may play an important role in the metastasis of HCC by promoting the migration of tumor cells.     

The CXCR4/CXCL12 (SDF-1) signalling pathway protects non-obese diabetic mouse from autoimmune diabetes

Chemokines and their receptors are part of polarized T helper 1 (Th1)- and Th2-mediated immune responses which control trafficking of immunogenic cells to sites of inflammation. The chemokine stromal cell-derived factor-1 CXCL-12 (SDF-1) and its ligand the CXCR4 chemokine receptor are important regulatory elements. CXCR4 is expressed on the surface of CD4(+) T cells, dendritic cells and B lymphocytes. Levels of CXCR4 mRNA were increased in pancreatic lymph nodes (PLNs) of 4-week-old non-obese diabetic (NOD) mice in comparison to Balb/C mice. However, a significant reduction of CXCR4 was noticed at 12 weeks both at the mRNA and protein levels while expression increased in the inflamed islets. The percentage of SDF-1 attracted splenocytes in a transwell chemotaxis assay was significantly increased in NOD versus Balb/c mice. SDF-1 attracted T cells completely abolished the capacity of diabetogenic T cells to transfer diabetes in the recipients of an adoptive cell co-transfer. When T splenocytes from NOD females treated with AMD3100, a specific CXCR4 antagonist, were mixed with diabetogenic T cells during adoptive cell co-transfer experiments, prevalence of diabetes in the recipients rose from 33% to 75% (P < 0.001). This effect was associated with an increase of interferon (IFN)-gamma mRNA and a reduction of interleukin (IL)-4 mRNA levels both in PLNs and isolated islets. AMD3100 also reduced IL-4 and IL-10 production of plate-bound anti-CD3 and anti-CD28-stimulated splenocytes. Immunofluorescence studies indicated that AMD3100 reduced the number of CXCR4(+) and SDF-1 positive cells in the inflamed islets. We can conclude that the CXCL-12/CXCR4 pathway has protective effects against autoimmune diabetes.     

过表达CXCR4/CXCR7影响人脐带间充质干细胞迁移和增殖

目的探讨SDF-1/CXCR4及SDF-1/CXCR7对人脐带间充质干细胞(h UC-MSCs)迁移和增殖活性的影响。方法用Ad-EASY腺病毒质粒系统分别构建表达CXCR4和CXCR7的重组腺病毒,感染h UC-MSCs后用FCM分别检测细胞膜的CXCR4和CXCR7受体的表达,Transwell法检测细胞迁移,MTT检测h UC-MSCs增殖活性,以及在H2O2诱导细胞毒性作用对细胞存活的影响。结果成功构建表达人源的CXCR4和CXCR7的重组腺病毒,感染后h UC-MSCs细胞膜上的CXCR4/CXCR7受体阳性表达率分别达到93.7%和78.5%(P0.01),高表达CXCR4和CXCR7均显著增强SDF-1诱导的h UC-MSCs细胞迁移,其中CXCR7效应稍弱;高表达CXCR7而不是CXCR4显著提高SDF-1诱导的h UC-MSCs增殖活性和氧化应激状态下的细胞存活率(P0.05)。结论 CXCR4/CXCR7均参与介导了SDF-1诱导的h UC-MSCs细胞迁移作用,同时CXCR7还介导了SDF-1诱导的h UC-MSCs增殖和H2O2处理损伤的保护。     

Neutrophils promote motility of cancer cells via a hyaluronan-mediated TLR4/PI3K activation loop

Inflammation is a component of tumour progression mechanisms. Neutrophils are a common inflammatory infiltrate in many tumours, but their regulation and functions in neoplasia are not understood. We recently demonstrated that pro-inflammatory IL-17-producing cells recruited blood neutrophils into the peritumoural stroma of hepatocellular carcinoma by epithelium-derived CXC chemokines. Here we show that a substantial population of neutrophils accumulates in the peritumoural stroma of hepatocellular, cervical, colorectal, and gastric carcinomas, and that this correlates with metastases in hepatocellular and gastric carcinomas. Exposure of neutrophils to culture supernatants from several types of solid tumour cells (TSN) resulted in sustained survival and pro-tumourigenic effects of cells. Kinetic experiments reveal that, shortly after exposure to TSN, neutrophils began to provoke activation and then produced significant inflammatory cytokines and expressed more anti-apoptotic Mcl-1 but less pro-apoptotic Bax. These long-lived neutrophils effectively enhanced the cancer cell motility via a contact-dependent mechanism; this effect, together with early activation and subsequent longevity of TSN-exposed neutrophils, could be reversed by blocking the activation of PI3K/Akt signalling in neutrophils. Moreover, we found that hyaluronan (HA) fragments constitute a common factor produced by various tumours that mimics the effect of TSN to induce long-lived neutrophils and subsequent malignant cell migration. The effects of TSN were inhibited by function blocking interactions between HA and its receptor TLR4 on neutrophils, suggesting that this is a key signalling pathway involved. These results indicate that HA derived from malignant cells educates neutrophils to adopt an activated phenotype, and in that way stimulates the metastasis of malignant cells, which represents a positive regulatory loop between tumours and their stroma during neoplastic progression.     

CXCL12-CXCR4/CXCR7轴信号传导通路与肿瘤细胞生物学特性的关系

越来越多的研究表明CXCR4与CXCR7在肿瘤的发生发展过程中发挥着重要作用,CXCR4与CXCR7作为G蛋白藕联受体介导的信号传导通路及其在胞内激化级联信号通路与肿瘤发生发展的分子机制有密切关系。本文将对它们各自介导的信号通路及其在胞内的级联信号通路与肿瘤细胞的生长、增殖、黏附和迁移等生物学特性的关系进行综述。     

骨碎补总黄酮依赖PI3K/Akt通路与牙髓干细胞的成骨分化

背景：PI3K/Akt通路可能在骨碎补总黄酮促成骨分化作用中发挥重要调控作用。 目的：观察骨碎补总黄酮对大鼠牙髓干细胞成骨分化的影响,并对PI3K/Akt通路在其中的作用进行初步探讨。 方法：采用组织块消化法获得大鼠牙髓细胞,克隆化分离培养大鼠牙髓干细胞并进行鉴定。在培养体系中加入不同质量浓度(0.01,0.05,0.1 g/L)的骨碎补总黄酮,观察各组细胞的碱性磷酸酶水平及钙结节形成情况,并用Western Blot法检测各组细胞磷酸化Akt的表达变化。 结果与结论：分离得到的牙髓干细胞的细胞表面标志CD44和CD29呈阳性表达,而CD34表达呈阴性。骨碎补总黄酮组牙髓干细胞的碱性磷酸酶活性、钙结节形成能力和磷酸化Akt蛋白相对表达量增加,较空白对照组差异有显著性意义,且随骨碎补总黄酮质量浓度的增加而升高,表现出一定浓度和时间依赖性。说明骨碎补总黄酮对大鼠牙髓干细胞成骨分化具有促进作用,且该作用可能是依赖PI3K/Akt通路所介导的。     

Role of TM4SF1 in regulating breast cancer cell migration and apoptosis through PI3K/AKT/mTOR pathway

Purpose: The purpose of this study was to investigate the effect of transmembrane-4-l-six-family-1 (TM4SF1) on breast cancer cell line MDA-MB-231 invasion and apoptosis and its mechanism through PI3K/AKT/mTOR pathway. Methods: siRNA-TM4SF1 and pcDNA-TM4SF1 plasma were constructed and then transfected into MDA-MB-231 cells respectively. Real time (RT)-PCR was used to measure the mRNA expression of TM4SF1 in each group. Also, matrigel method and Annexin V-FITC were used to detect the effect of TM4SF1 expression on MDA-MB-231 cell migration and apoptosis respectively. Besides, western blotting analyze was used to assay the effects of TM4SF1 expression on PI3K/AKT/mTOR pathway associated proteins expressions. Results: The results showed that after being transfected with siRNA-TM4SF1, TM4SF1 expression was significantly declined, while it was significantly increased after cells were transfected with pcDNA-TM4SF1 (P<0.05). Compared with the controls, TM4SF1 overexpression significantly contributed MDA-MB-231 cell migration but decreased apoptotic cells (P<0.05), which were opposite to the results when TM4SF1 was sliced in cells. Moreover, TM4SF1 slicing significantly decreased the expressions of phosphorylated (p)-AKT, p-mTOR, and p-P70 (P<0.05). Conclusion: Our study suggested that TM4SF1 may be a therapeutic target for breast cancer treatment and may loan insight into the mechanisms behind the development and metastasis of advanced breast cancer.     

CXCR4–CXCL12 interaction is important for plasma cell homing and survival in NZB/W mice

Antibody‐secreting cells (ASCs), including short‐lived plasmablasts and long‐lived memory plasma cells (LLPCs), contribute to autoimmune pathology. ASCs, particularly LLPCs, refractory to conventional immunosuppressive drugs pose a major therapeutic challenge. Since stromal cells expressing C‐X‐C motif chemokine‐12 (CXCL12) organize survival niches for LLPCs in the bone marrow, we investigated the effects of CXCL12 and its ligand CXCR4 (C‐X‐C chemokine receptor 4) on ASCs in lupus mice (NZB/W). Fewer adoptively transferred splenic ASCs were retrieved from the bone marrow of recipient immunodeficient Rag1^?/? mice when the ASCs were pretreated with the CXCR4 blocker AMD3100. CXCR4 blockade also significantly reduced anti‐OVA ASCs in the bone marrow after secondary immunization with OVA. In this study, AMD3100 efficiently depleted ASCs, including LLPCs. After two weeks, it decreased the total number of ASCs in the spleen and bone marrow by more than 60%. Combination with the proteasome inhibitor bortezomib significantly enhanced the depletion effect of AMD3100. Continuous long‐term (five‐month) CXCR4 blockade with AMD3100 after effective short‐term LLPCs depletion kept the number of LLPCs in the bone marrow low, delayed proteinuria development and prolonged the survival of the mice. These findings identify the CXCR4‐CXCL12 axis as a potential therapeutic target likely due to its importance for ASC homing and survival.     

SDF-1/CXCR4轴通过调控间充质干细胞定向分化修复缺氧缺血性脑损伤

目的:探讨基质细胞衍生因子-1(stromalcell-derivedfactor-1,SDF-1)/CXC趋化因子受体4(CXCchemokinereceptor4,CXCR4)轴调控间充质干细胞定向分化、修复缺氧缺血性脑损伤的作用。方法:大鼠间充质干细胞(ratmesenchymalstemcells,rMSCs)经缺氧培养不同时点(0h、6h、12h、24h、48h、72h)或SDF-1α(10μg/L)孵育后,采用RT-PCR、Westernblotting和流式细胞术检测其表面CXCR4表达的变化;建立大鼠缺氧缺血性脑损伤模型,运用RT-PCR和Westernblotting检测造模后不同时点(1d、3d、5d、7d、14d、21d)大鼠脑部海马组织中SDF-1αmRNA转录和蛋白表达的改变情况;用AMD3100(CXCR4拮抗剂)拮抗rMSCs表面CXCR4后,免疫细胞化学和Westernblotting检测rMSCs诱导向神经细胞分化中神经元特异性烯醇化酶(neuron-specificenolase,NSE)和胶质纤维酸性蛋白(glialfibrillaryacidicprotein,GFAP)等神经细胞特异性标志物的阳性率及表达变化情况。结果:低氧培养6h及12h的rMSCsCXCR4mRNA及蛋白表达水平均较常氧培养组明显增加(P<0.01),10μg/LSDF-1α孵育后rMSCs的CXCR4表达水平明显增加(P<0.01);缺氧缺血性脑损伤模型的大鼠脑内SDF-1α蛋白表达显著增加(P<0.01);5mg/LAMD3100处理后的rMSCs在向神经细胞诱导分化中NSE和GFAP蛋白的表达明显减少。结论:微小剂量的SDF-1α可诱导低氧培养的rMSCs表面CXCR4的表达,而在缺氧缺血性脑损伤模型的大鼠脑内SDF-1α表达增加,从而使SDF-1/CXCR4轴的生物学效应得以增强;CXCR4拮抗的rMSCs在分化中神经细胞特异性标志物NSE和GFAP的表达降低,表明SDF-1/CXCR4轴在rMSCs定向神经分化修复缺血缺氧脑损伤中具有重要的调控作用。     

PI3K/Akt通路在低氧诱导脂肪干细胞增殖和向内皮细胞分化中的作用

文题释义：PI3K/Akt信号通路：Akt是PI3K/Akt信号转导通路的核心,其分子质量约为60 kD,是原癌基因c-akt表达编码的一种丝氨酸/苏氨酸蛋白激酶。外源性抑制剂LY294002或wortmannin均可负向调节PI3K/Akt信号通路,导致第二信使PIP3逆行转化为PIP2,阻断其调节作用。 低氧：氧体积分数是机体微环境的重要组成部分,直接影响着细胞的成活和生物学行为。在体外培养过程中氧体积分数为1%-5%时即可为脂肪干细胞的增殖和功能提供足够的刺激,同时维持细胞形态和多向分化能力不变,因此可以认为低氧环境可以更好地为干细胞特性的维持提供信号传导。 背景：大量研究证明低氧可以促进干细胞的增殖和分化,但目前尚不清楚其通过何种途径发挥作用。 目的：观察低氧对脂肪干细胞增殖和向内皮细胞分化的影响,并探讨PI3K/Akt通路在此过程中的作用。 方法：取培养至第3代的Wistar大鼠脂肪干细胞,分为常氧组、低氧组、低氧+LY294002组,3组均在体积分数为20%O₂培养箱中培养24 h,然后低氧组转移至体积分数为2%O₂培养箱中进行培养,常氧组继续在体积分数为20%O₂培养箱中培养,低氧+LY294002组在低氧培养环境下的细胞培养基中加入终浓度为25 mmol/L的PI3K/Akt通路抑制剂LY294002。培养24 h后,Western blot检测p-Akt的表达明确PI3K/Akt通路的激活情况;CCK-8法检测各组脂肪干细胞的增殖情况;各组脂肪干细胞加入血管内皮细胞诱导培养基进行诱导分化10 d,分别通过qRT-PCR及抗CD31免疫荧光染色检测各组脂肪干细胞分化为内皮细胞的情况。 结果与结论：①第3代脂肪干细胞呈现出典型的梭形结构,流式细胞仪检测结果显示CD34和CD45表达阴性,CD105表达阳性,并可向成骨及成脂细胞方向分化;②低氧培养条件下p-Akt的表达明显升高,加入LY294002后p-Akt的表达受到明显抑制;③低氧组细胞增殖率明显高于常氧组和低氧+LY294002组(P < 0.05),低氧+ LY294002组脂肪干细胞的增殖率低于低氧组(P < 0.05);④低氧组内皮细胞基因及特异性蛋白CD31的表达明显高于常氧组和低氧+LY294002组(P < 0.05),低氧+LY294002组内皮细胞基因及特异性蛋白CD31的表达低于低氧组(P < 0.05),但仍高于常氧组(P < 0.05);⑤结果证实PI3K/Akt通路在低氧诱导的脂肪干细胞增殖及向内皮细胞分化过程中发挥重要作用。 ORCID: 0000-0001-8454-263X(殷令妮) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

子宫颈病变组织中HPV 16感染与TLR4介导的PI3 K/AKT信号通路相关蛋白表达的关系

目的：探讨子宫颈病变中Toll样受体4(Toll-like receptors 4, TLR4)介导的PI3K/AKT信号通路相关蛋白表达与人乳头状瘤病毒(human papillomavirus HPV)16感染的关系。方法采用免疫组化SP法检测152例慢性子宫颈炎、子宫颈上皮内瘤变(cervical intra-epithilial neoplasia, CIN)以及子宫颈鳞状细胞癌组织中TLR4、PI3K、AKT、NF-κB蛋白的表达;抽提石蜡组织总DNA,用PCR法检测组织中HPV 16的感染情况。结果在慢性子宫颈炎、CIN和子宫颈鳞状细胞癌组织中TLR4、PI3K、AKT和NF-κB 蛋白阳性率分别为32．0%、59．4%、77．8%,28．0%、56．3%、73．0%,24．0%、56．3%、79．4%,8．0%、48．4%、81．0%,并且随着子宫颈病变的加重表达增强(P<0．05);HPV 16在3组子宫颈病变组织中的感染率分别为8．0%、48．4%和81．0%(P<0．05)。 TLR4、PI3K、NF-κB蛋白及HPV 16均与子宫颈癌分化程度有关(P<0．05);PI3K和AKT与临床分期密切相关,NF-κB与淋巴结转移有关(P<0．05);在CIN和子宫颈鳞状细胞癌组织中TLR4分别与HPV 16(r=0．303,P=0．015;r=0．633,P=0．000)和PI3K(r=0．254,P=0．045;r=0．386,P=0．003)密切相关;在子宫颈鳞状细胞癌组织中PI3K与AKT密切相关(r=0．298,P=0．018)。结论 HPV 16感染上调TLR4在CIN中的表达,TLR4介导的PI3K/AKT信号通路共同作用对子宫颈上皮从炎症→CIN→子宫颈癌过程中发挥重要作用,HPV 16的感染可能是影响通路分子表达改变的前提条件。     

归肾丸水提物干预SD大鼠骨髓间充质干细胞增殖及PI3K、AKT蛋白的表达

文题释义：归肾丸：归肾丸原方出自《景岳全书》,全方由熟地、杜仲、山药、枸杞子、菟丝子、茯苓、当归、酒萸肉8味药组成,有补肾填精、调理冲任的功效,常用于治疗妇科疾病。作者采用纯水煎煮的方法获取归肾丸,所制得的归肾丸冻干粉1 g含生药量约为5.2 g。原代骨髓间充质干细胞：原代细胞是指直接从机体取下细胞、组织和器官后立即进行培养,传代前保持原有细胞的基本性质,通常把第1代至第10代以内的细胞统称为原代细胞。该实验从3周龄雄性SD大鼠的双侧股骨骨髓获取原代骨髓间充质干细胞,经200目筛网过滤后,用全骨髓贴壁法纯化,经鉴定后选取纯度和增殖能力均较高的第3代细胞进行后续实验。背景：补肾类方剂对骨髓间充质干细胞的促增殖作用已经被证实,但其作用机制尚不明确,该研究以归肾丸为例,探讨其可能的作用机制。目的：通过观察归肾丸水提物对骨髓间充质干细胞增殖的影响,探究归肾丸滋补肾精与骨髓间充质干细胞增殖之间的关系。方法：从3周龄雄性SD大鼠股骨骨髓中分离提取骨髓间充质干细胞,采用全骨髓贴壁法将其纯化,选用纯度较高的第3代细胞进行药物干预,将其分为空白对照组和10,20,40,80,100 mg/L归肾丸水提物组,在体外连续培养5 d以观察量效关系和时效关系。倒置显微镜下观察细胞形态,CCK-8法评估细胞增殖活性,Western blot检测细胞中PI3K、AKT蛋白表达。结果与结论：①归肾丸水提物组的细胞增殖能力明显高于空白对照组,存在一定的量效和时效关系,尤以   80 mg/L归肾丸水提物干预3 d时作用效果最佳;②归肾丸水提物组骨髓间充质干细胞中PI3K、AKT蛋白的表达明显高于空白对照组;③结果提示,归肾丸水提物能有效促进骨髓间充质干细胞的增殖,可能与其参与调控PI3K/AKT信号通路有关。ORCID: 0000-0003-0720-4797(刘燕)中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Prostaglandin transporter,SLCO2A1, mediates the invasion and apoptosis of lung cancer cells via PI3K/AKT/mTOR pathway

Treatment of lung cancer involves regulation of various key factors in many signaling pathways. The prostaglandin transporter, solute carrier organic anion transporter family member 2A1 (SLCO2A1), is a promising regulatory factor of cancer cells. By analyzing the invasion and apoptosis status of lung cancer cells, and detecting the expression changes of key factors in PI3K/AKT/mTOR pathway after overexpression and knockdown of SLCO2A1 in vitro, this study intended to investigate the function of SLCO2A1 in mediating lung cancer cells. Results showed overexpression of SLCO2A1 could induce the invasion of lung cancer cells, and its knockdown inhibited the invasion and induced the apoptosis of cells. mTOR, AKT and S6 in PI3K/AKT/mTOR pathway were not affected by SLCO2A1. But the expression levels of p-mTOR, p-AKT and p-S6 were up-regulated or down-regulated with the overexpression or knockdown of SLCO2A1. Thus SLCO2A1 was inferred to mediate the invasion and apoptosis of lung cancer cells via PI3K/AKT/mTOR pathway. These results implied SLCO2A1 could be a regulatory factor of the invasion and apoptosis of lung cancer cells and serve as a promising target for lung cancer therapy.     

Hypoxia activates the PI3K/AKT/HIF-1α pathway to promote the anti-inflammatory effect of adipose mesenchymal stem cells

This study aimed to investigate the effect of hypoxia on the anti-inflammatory effect of adipose-derived mesenchymal stem cells (AMSCs) in vitro and its possible mechanism. AMSCs were cultured in vitro in a hypoxic environment with 3% O₂, and a normoxic (21% O₂) environment was used as the control. The cells were identified by in vitro adipogenic and osteogenic differentiation and cell surface antigen detection, and the cell viability were detected. The effect of hypoxic AMSCs on macrophage inflammation was analyzed by co-culture. The results showed that under hypoxia, AMSCs had better viability, significantly downregulated the expression of inflammatory factors, alleviated macrophage inflammation, and activated the PI3K/AKT/HIF-1α pathway.