Treatment of gastrointestinal neuroendocrine tumors with inhibitors of growth factor receptors and their signaling pathways: Recent advances and future perspectives

The limited efficacy of conventional cytotoxic treatment regimes for advanced gastrointestinal neuroendocrine cancers emphasizes the need for novel and more effective medical treatment options. Recent findings on the specific biological features of this family of neoplasms has led to the development of new targeted therapies, which take into account the high vascularization and abundant expression of specific growth factors and cognate tyrosine kinase receptors. This review will briefly summarize the status and future perspectives of antiangiogenic, mTOR- or growth factor receptor-based pharmacological approaches for the innovative treatment of gastrointestinal neuroendocrine tumors. In view of the multitude of novel targeted approaches, the rationale for innovative combination therapies, i.e. combining growth factor (receptor)-targeting agents with chemo- or biotherapeutics or with other novel anticancer drugs such as HDAC or proteasome inhibitors will be taken into account.

Effect of grape proanthocyanidins on tumor growth and angiogenesis in H22 liver cancer xenograft model

Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.

Dicranostigma leptopodum (maxim) fedde induced apoptosis in SMMC-7721 human hepatoma cells and inhibited tumor growth in mice

Dicranostigma Leptopodum (Maxim) Fedde (DL- F), which had been previously documented to suppress oxidative hemolysis of erythrocytes and enhance immune functions of murine peri- toneal macrophages, was investigated for its effect on anti-tumor activity. Of alkaloids extracted from DLF, five have been identified with employment of chromatographic analysis. An antiproliferative role of these alkaloids was determined on SMMC-7721 Human Hepatoma Ce- lls in an apoptosis-inducing manner, through MTT assaying, Trypan blue exclusion assaying and cytometric analysis of cell cycle distribution. To further examine their inhibitory effects on tumor progression, murine H22 cells were inoculated into Kunming mice to determine the role of these alkaloids of DLF in inhibiting tumor growth in the tumor-implanted mice. It was found that these alkaloids of DLF enhanced the tumor shrinkage effectively wherein its tumor inhibitory rate and immunohistochemistry stain- ing of the tumor were determined and profiled, respectively.

Trojan horses in tumor:engineered pyroelectric and photodynamic nanocomposites for NIR-induced cell apoptosis and tumor growth inhibition

It is desirable but always challenging to develop a cutting-edge tumor treatment strategy with high therapeutic efficacy,lesiontargeted precision and mild accessibility.Compared to traditional treatment modalities,photodynamic therapy has been widely studied since the generation of reactive oxygen species(ROS)at cancerous lesions unprecedentedly offers a convenient approach for localized tumor eliminations.Nevertheless,the consumption of oxygen for ROS production in a hypoxic tumor microenvironment has dramatically limited its feasibility and efficacy.Herein,the engineered nanocomposites of BTO@PDA-ICGHA with photodynamic and pyroelectric performances have been fabricated and applied to the photodynamic-pyroelectric dynamic treatments.The continuing ROS production derived from intracellular oxygen(O_(2))and water(H_(2)O)by laser irradiation contributed to the superb tumor cell apoptosis and significant tumor growth inhibition.Thus,this study has validated a new concept by depositing the engineered nanocomposites at the tumor just like Trojan horses,facilitating ROS release as killers and exerting the NIR-induced cell apoptosis and tumor growth inhibition with high therapeutic efficiency and expectable translational perspectives.

ANTITUMOR MECHANISM OF GEM10 BY THE NATURAL KILLER ACTIVITY AND INTERLEUKIN-2 PRODUCTION

Objective To investigate th e anti-tumor effects of GeM10 by the natural killer(NK) cells activities and th e production of Interleukin-2 (IL-2) in peripheral blood mononuclear cells (PB MNCs). Methods Assay of human NK cells activities by dye reject ion assay in vitro and production of IL-2 in PBMNC by IL-2 bioassay with I L-2 dependent cell line CTLL2 and MTT colorometric method. Results GeM10 could significantly stimulate NK activities (60μg·mL -1 G eM10: 17.077±7.665, 120μg·mL -1 GeM10: 24.9±13.04; control: 7.72±4 .64, P< 0.05). GeM10 could up-regulate the production of IL-2 of PBMNCs in tumor patients(60μg·mL -1 GeM10: 2.965± 1.183; 120μg·mL -1 GeM10: 2.28±0.847; control: 1.792±0.823, P<0.05).Conclu si on The GeM10 not only can stimulate the NK activities but also increase the IL-2 production by PBMNCs in tumor patients. These findings indicate that the GeM10 may have promise as an anti-tumor drug and a biological response modi fier in clinic.

Inhibitory effect of arsenic trioxide on angiogenesis and expression of vascular endothelial growth factor in gastric cancer

AIM: To investigate the inhibitory effect of As2O3 on angiogenesis of tumor and expression of vascular endothelial growth factor (VEGF) in tumor cells in vivo and in vitro. METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As2O3 was injected into the arsenic-treated groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected into the control group. Microvessel density (MVD) and expression of VEGF were detected with immunofluorescence laser confocal technology. Further expression of VEGF protein and VEGF mRNA was measured with Western bloting and fluorescence quantitative RT- PCR in SGC-7901 cells treated with As2O3. RESULTS: In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As2O3 respectively, about 50% and 30% tumor growth inhibition were observed correspondingly (P < 0.05, P < 0.05). Decrease in MVD appeared in As2O3-treated tumors compared with control group (P < 0.001, P < 0.001). MVD in tumors was significantly lower in 5 mg/kg group than in 2.5 mg/kg group (P < 0.01). The fluorescence intensity levels of VEGF in tumor cells were significantly lowered in the arsenic-treated groups (P < 0.01, P < 0.01). The fluorescence intensity level of VEGF in 5 mg/kg group was lower than that in 2.5 mg/ kg group (P < 0.01). In vitro, the expression of VEGF protein decreased in dose- and time-dependent manner after the treatment with As2O3, but in VEGF mRNA no significant difference was found between the control group and the treated groups. CONCLUSION: As2O3 can inhibit solid tumor growth by inhibiting the formation of new blood vessels. One of the mechanisms is that As2O3 can inhibit VEGF protein expression.

Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice

AIM： To investigate the effect of arsenic trioxide （As2O3） on expression of vascular endothelial growth factor receptor-1 （VEGFR-1, Flt-1） and VEGFR-2 （KDR） in human gastric tumor cells and proliferation of vascular endothelial cells.METHODS： The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density （MVD） and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy. SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 ＋ As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry.RESULTS： The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 μmol/L, respectively. Early apoptosis in the As2O3- treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls.CONCLUSION： Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.

C-reactive protein,procalcitonin,interleukin-6,vascular endothelial growth factor and oxidative metabolites in diagnosis of infection and staging in patients with gastric cancer

AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS:We examined the levels of serum VEGF,IL-6, PCT,CRP and plasma MDA,NO in 42 preoperative gastric cancer patients and 23 healthy subjects.There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS:The VEGF levels (mean±SD; pg/mL) were 478.05±178.29 and 473.85±131.24 in gastric cancer patients with and without infection,respectively,and these values were not significantly different (P>0.05).The levels of VEGF, CRP,PCT,It-6,MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP,PCT,It-6,MDA and NO were statistically increased in infection group when compared with non- infection group (P<0.001). CONCLUSION:Although serum VEGF concentrations were increased in gastric cancer,this increase might not be related to infection.CRP,PCT,IL-6,MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study,IL-6,MDA,NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.

EXPERIMENTAL STUDY OF THE EFFECT OF ANGIOGENESISINHIBITOR TNP-470 ON THE GROWTH AND METASTASISOF GASTRIC CANCER IN VIVO

Objective: To study the effect of angiogenesis inhibitor TNP-470 on the growth and metastasis of gastric cancer in vivo. Methods: Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact tumor tissue into gastric wall of nude mice. TNP-470 was administrated S.C. at doses of 0 mg/kg, 15 mg/kg, 30 mg/kg, 60 mg/kg every other day for eight weeks. Ten weeks after implantation, the mice were sacrificed and the tumor size measured and the presence of metastasis recorded. The microvascular density was examined by immunohistochemical staining with anti-human factor VIII antibody. Results: Compared to the untreated controls, growth of the orthotopically implanted tumor was significantly reduced in size in the mice treated with TNP-470 with an inhibition rate of 59.9%, 77.0% and 84.9% at the dosage of 15 mg/kg, 30 mg/kg and 60 mg/kg, respectively. Tumor metastasis to the liver and peritoneum was also significantly inhibited in a dose-dependent manner. The microvascular density was also decreased significantly in the treated mice. Conclusion: Angiogenesis inhibitor TNP-470 has strong inhibitory effect both on tumor growth and metastasis of human gastric cancer in nude mice.

鳖甲煎丸对肝癌大鼠黏着斑激酶/雷帕霉素靶蛋白通路的影响

目的:探讨鳖甲煎丸对肝癌模型大鼠肝组织病理特征及FAK/mTORC1通路的影响。方法:HepG2(1×10^(7))细胞注射于大鼠右腋皮下,建立肝癌模型,分为模型组、5-氟尿嘧啶组、鳖甲煎丸低剂量组、鳖甲煎丸高剂量组,另设正常组。各药物组给予相应药物灌胃,持续给药4周,正常组、模型组给予等体积的0.9%氯化钠溶液。实验结束后,测定肝癌组织重量、肝癌组织体积、肝癌组织抑瘤率、肝癌FAK、mTORC1水平、肝癌VEGFR-2、VEGF、IL-4、IL-8、TNF-α蛋白水平。结果:与正常组比较,模型组肝癌组织重量、肝癌组织体积、肝癌组织抑瘤率、VEGFR-2、VEGF、IL-4、IL-8、TNF-α蛋白、肝癌FAK、mTORC1 mRNA和蛋白表达升高(均P<0.05)。与模型组比较,5-氟尿嘧啶组、鳖甲煎丸低剂量组、鳖甲煎丸高剂量组肝癌组织重量、肝癌组织体积、肝癌组织抑瘤率、VEGFR-2、VEGF、IL-4、IL-8、TNF-α蛋白、肝癌FAK、mTORC1 mRNA和蛋白表达降低(均P<0.05)。鳖甲煎丸高剂量组肝癌组织重量、肝癌组织体积、肝癌组织抑瘤率、VEGFR-2、VEGF、IL-4、IL-8、TNF-α蛋白、肝癌FAK、mTORC1 mRNA和蛋白表达低于鳖甲煎丸低剂量组(均P<0.05)。结论:鳖甲煎丸对大鼠肝癌具有明显抑制作用,能减轻大鼠肝癌所致的病理损伤,其机制可能与鳖甲煎丸抑制肝癌FAK、mTORC1表达,诱导肝癌细胞凋亡,降低炎症反应有关。

基于PI3K/AKT信号通路探讨汉黄芩素对宫颈癌HeLa细胞移植瘤抑制作用影响

目的探究汉黄芩素对宫颈癌HeLa细胞移植瘤的抑制作用及机制。方法随机选取2018年1月—2020年12月常熟市中医院的50只Balb/c小鼠进行宫颈癌荷瘤模型造模,随机分为5组:模型对照组、阳性对照组、小剂量组、中剂量组及大剂量组。模型对照组不做特殊处理,阳性对照组腹腔注射25 mg/kg环磷酰胺,小剂量组、中剂量组、大剂量组小鼠灌胃25 mg/kg、50 mg/kg、100 mg/kg汉黄芩素。处死小鼠取出瘤体,比较各组肿瘤质量、体积,计算肿瘤生长抑制率;取出胸腺、脾脏并计算相关脏体指数。将小鼠肿瘤分为两份,一份采用伊红-美兰(HE)染色进行组织学观察;另一份采用免疫印迹法检测各组小鼠PI3K、AKT、p-AKT表达情况。结果阳性对照组的肿瘤生长抑制率为69.63%,大剂量组、中剂量组、小剂量组的肿瘤生长抑制率分别为77.78%、54.81%和31.85%均高于模型对照组,差异有统计学意义(P<0.05)。大剂量组肿瘤生长抑制率为77.78%高于阳性对照组,差异有统计学意义(P<0.05)。免疫印迹法结果显示,与模型对照组比较,大剂量组、中剂量组与小剂量组PI3K、AKT及p-AKT蛋白表达均显著降低,差异有统计学意义(P<0.05);高剂量组与阳性对照组PI3K、AKT和p-AKT表达量接近,差异有统计学意义(P<0.05)。结论汉黄芩素对宫颈癌Hela细胞移植瘤生长具有明显抑制作用,其作用机制可能通过抑制PI3K/AKT通路与诱导细胞凋亡有关。

紫铆素经EGFR-STAT3信号通路对荷宫颈癌裸鼠肿瘤生长的影响

目的探讨紫铆素对荷宫颈癌裸鼠肿瘤生长与肿瘤组织表皮生长因子受体(EGFR)、信号转导和转录激活因子3(signal transducer and activator of ranscription 3,STAT3)表达的影响。方法裸鼠左侧腑下接种宫颈癌SiHa细胞的方法构建宫颈癌模型,将成功构建的荷宫颈癌裸鼠随机分为模型组、阳性药组与低、中、高剂量组,每组各12只。低、中、高剂量组裸鼠分别给予11.5 mg/ml、46 mg/ml、115 mg/ml注射剂量的紫铆素注射,阳性药组给予4.3 ml/kg剂量的顺铂注射,模型组给予等量生理盐水;每天1次,连续注射7 d后,观察1周。测定各组裸鼠的抑瘤率及肝脏指数、肾脏指数;HE染色形态学观察肿瘤的病理特点,免疫组化、RT-qPCR检测肿瘤组织中EGFR、STAT3的表达水平。结果抑瘤率分析阳性药组(60.82±7.30%)和高剂量组(49.30±10.42)高于低、中剂量组,肿瘤体积与瘤重低于低、中剂量组和模型组;肾脏指数分析阳性药组(10.25±0.48)和高剂量组(10.13±0.47)低于模型组和低、中剂量组;EGFR蛋白表达阳性药组(0.002±0.002)、高剂量组(0.012±0.008)和STAT3蛋白表达阳性药组(0.063±0.011)、高剂量组(0.099±0.013)显著低于模型组和低、中剂量组;EGFR基因表达阳性药组(0.462±0.092)、高剂量组(0.524±0.115)和STAT3蛋白相对表达量阳性药组(0.435±0.123)、高剂量组(0.593±0.092)显著低于模型组和低、中剂量组;病理特点显示阳性药组、高剂量组肿瘤组织坏死情况较模型组和低、中剂量组明显降低;以上指标,差异有统计学意义(P<0.05)。结论紫铆素可有效抑制宫颈肿瘤的生长,且无明显毒性作用,其机制可能与宫颈肿瘤组织EGFR、STAT3表达相关。

古草生机汤对H22荷瘤小鼠体内抑瘤及免疫调节作用的初步研究

目的:探究古草生机汤对H22荷瘤小鼠体内实体瘤的抑瘤功效和对机体的免疫调节作用机制。方法:本研究采用H22实体瘤动物模型,随机分为空白组、模型组、阳性药组、古草生机汤低、高剂量组,灌胃给药7 d,计算各组小鼠的体质量增长率、肿瘤抑制率、胸腺及脾指数,小鼠实体瘤病理切片苏木精-伊红(HE)染色观察瘤体组织和细胞形态,酶联免疫吸附试验法检测小鼠血清中γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)、Fas、Fas配体、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)的含量,实时荧光定量PCR测量小鼠瘤组织中Bax和Bcl-2mRNA的相对表达量。结果:古草生机汤有促进H22荷瘤小鼠体质量增长、抑制体内实体瘤增长和促进肿瘤凋亡坏死的作用,可提高小鼠的胸腺指数同时降低脾脏指数,可显著提高小鼠血清中IFN-γ、TNF-α、IL-2的含量并降低Fas、Fas配体、AST、ALT的含量(均P<0.01),能够上调小鼠瘤组织中Bax mRNA的表达并下调Bcl-2mRNA的表达。结论:古草生机汤具有明显的体内抗肝肿瘤药效,在抑制肿瘤生长、促进肿瘤细胞凋亡、调节机体免疫方面有一定作用。

灵芝破壁孢子粉的抗肿瘤活性研究

目的研究灵芝破壁孢子粉对乳腺癌和口腔癌生长的抑制作用。方法采用灵芝破壁孢子粉乙醇提取物处理乳腺癌MCF-7细胞、口腔癌KB细胞和宫颈癌HeLa细胞,检测三种细胞的增殖情况。构建裸鼠乳腺癌MCF-7移植瘤和口腔癌KB移植瘤模型,评价灵芝破壁孢子粉进行灌胃治疗后的肿瘤生长抑制情况。结果灵芝破壁孢子粉乙醇提取物显著抑制MCF-7、KB和HeLa细胞的增殖,且该抑制效应呈剂量依赖性。在MCF-7移植瘤模型中,低、中、高3组灵芝破壁孢子粉给药剂量均有显著的肿瘤生长抑制作用,肿瘤抑制率分别为50.35%、65.72%和80.55%;但在KB移植瘤模型中,低剂量组没有显示显著的肿瘤生长抑制作用,而中剂量组和高剂量组表现出明显的抗肿瘤作用,3组肿瘤抑制率分别为4.03%、37.63%和40.59%。结论灵芝破壁孢子粉能够抑制MCF-7乳腺癌和KB口腔癌荷瘤裸鼠肿瘤的生长。

槲皮素通过生长抑制特异性基因5调节微小RNA-23a-3p和磷脂酰肌醇3激酶/蛋白激酶B信号通路抑制垂体神经内分泌肿瘤的增殖机制

目的:探讨槲皮素对垂体神经内分泌肿瘤(PitNETs)生长的抑制作用及其可能机制。方法:通过Starbase工具预测生长抑制特异性基因5(GAS5)与微小RNA-23a-3p(miR-23a-3p)结合情况,双荧光素酶报告实验和RNA免疫沉淀测定GAS5和miR-23a-3p之间的结合关系。体外培养人垂体瘤细胞系RC-4B/C,分为对照组(Control)、槲皮素组(Quercetin)、GAS5抑制组(Si-GAS5)和槲皮素+si-GAS5组(Quercetin+si-GAS5),对比分析槲皮素对GAS5、miR-23a-3p及磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)信号通路的影响,以及人垂体瘤复苏细胞(RC-4B/C)生长和侵袭能力的影响。结果:Starbase工具预测GAS5与miR-23a-3p结合,双荧光素酶报告实验和RNA免疫沉淀测定揭示了GAS5和miR-23a-3p之间的直接结合。槲皮素促进GAS5的表达,抑制miR-23a-3p和PI3K/AKT的表达,抑制RC-4B/C细胞的增殖和侵袭(均P<0.05);下调GAS5、miR-23a-3p表达增多,促进RC-4B/C细胞的增殖和侵袭(均P<0.05);槲皮素可以逆转GAS5下调引起的miR-23a-3p、PI3K/AKT表达增加,抑制RC-4B/C细胞的增殖和侵袭(均P<0.05)。结论:槲皮素可能通过促进GAS5表达竞争性抑制miR-23a-3p,降低了PI3K/AKT,抑制垂体神经内分泌肿瘤的生长。

功能性壳寡糖在食品领域的应用研究进展

壳寡糖主要以壳聚糖为原料,经生物酶解加工而成,具有分子量小、聚合度低、水溶性好等特点,分子量小于3000 Da的壳寡糖很容易通过肠道代谢被肠上皮吸收,具有多种生物功能活性。该文就小分子量的壳寡糖在调节肠道菌群、提高免疫力、抗肿瘤、保护肝脏、降尿酸、降血糖等方面的功能活性进行综述,对小于3000 Da分子量壳寡糖的功能活性进行比较分析,并充分探究不同分子量和聚合度的壳寡糖的作用机制,结合目前壳寡糖的应用现状,分析壳寡糖未来的发展趋势,为壳寡糖在食品等领域的广泛应用提供参考。

岩藻多糖纳米硒的制备及其抑制肿瘤细胞增殖的研究

探索岩藻多糖纳米硒(fucoidan-selenium nanoparticles,FD-SeNPs)的制备工艺条件,并进一步对其进行结构表征和抑制肿瘤细胞增殖的研究。以岩藻多糖(fucoidan,FD)为模板,采用抗坏血酸(ascorbic acid,Vc)还原亚硒酸钠(Na_(2)SeO_(3))制备FD-SeNPs,通过单因素和响应面实验优化其工艺参数。采用傅里叶变换红外光谱仪(FT-IR)、扫描电子显微镜(SEM)、能量色散X射线谱仪(EDX)、透射电子显微镜(TEM)和X射线衍射仪(XRD)对其进行结构表征;运用MTT法测定其对HepG2肝癌细胞和A549肺癌细胞存活率的影响。结果表明,FD-SeNPs的最佳制备工艺参数为:反应时间为1 h、反应温度为35℃、抗坏血酸与亚硒酸钠的摩尔比为14∶1、FD浓度为0.8 mg/mL,在此条件下制备得到的FD-SeNPs粒径为(83.40±0.55)nm、电位为(-31.89±0.47)mV、含硒量达29.93%。经鉴定,FD-SeNPs的表面形貌为均一的球形,由77.59%Se、17.70%C和3.41%O元素组成。MTT实验结果表明,FD-SeNPs能显著抑制HepG2肝癌细胞和A549肺癌细胞的增殖,具有良好的剂量效应。上述结果表明,已成功制备FD-SeNPs并表现出一定的抑制肿瘤细胞增殖的能力,为其在抗肿瘤临床药物的应用开发提供了一定的技术手段和理论数据参考。

二烯丙基三硫对胃癌MGC-803细胞的生长抑制作用

目的 研究二烯丙基三硫 (DATS)在体外对胃癌MGC 80 3细胞的生长抑制作用。方法 采用MTT法、集落形成率及生长曲线绘制分别观察不同浓度DATS对胃癌MGC 80 3细胞生长的影响。结果 DATS处理后 ,培养的MGC 80 3细胞增殖抑制而稀少。不同浓度DATS对胃癌MGC 80 3细胞的作用 ,4、8、12、16、2 4mg·L-1的细胞生长抑制率分别为 2 6 %、4 6 %、6 5 %、76 %、89% ,其半数抑制浓度(IC50 )为 8 2mg·L-1。 8、12、16、2 4mg·L-1的细胞集落形成率和集落形成相对数各为 32 4 %和 5 8 7%、2 4 8%和4 2 5 %、19%和 33 5 %、8 8%和 15 1% ,皆具有明显的量效关系 ,且随着浓度增高 ,细胞生长曲线趋于低平。结论 DATS在体外对胃癌MGC 80

垫状卷柏总黄酮的抗氧化和抗肿瘤活性

目的:研究垫状卷柏总黄酮的抗氧化能力,以及对人宫颈癌细胞Hela、人乳腺癌细胞MDA-MB-231、人前列腺癌细胞PC-3M的生长抑制作用。方法:采用Fenton法、邻苯三酚自氧化法、DPPH法和还原力测定法评价垫状卷柏总黄酮的体外抗氧化能力。CCK-8法检测垫状卷柏总黄酮的抗肿瘤细胞增殖活性。结果:在总黄酮质量浓度为20~100μg/m L之间,垫状卷柏总黄酮对羟基自由基、超氧阴离子自由基、DPPH自由基的清除率随总黄酮质量浓度升高而增高,半数清除率EC_(50)分别为111.86、89.24、26.51μg/m L;对Hela、PC-3M和MDA-MB-231细胞的抑制作用在总黄酮质量浓度为6.59~79.02μg/m L范围内均呈剂量依赖性,作用时间为72 h的抑制率高于48 h的抑制率。结论:垫状卷柏总黄酮抗氧化活性作用能力强,对Hela、PC-3M和MDA-MB-231细胞具有显著的增殖抑制作用。