BACKGROUND:The glucose transporter-1(Glut-1),a key ratelimiting factor in the transport and metabolism of glucose in cancer cells,is over-expressed in many human cancer cells and this overexpression is correlated with...BACKGROUND:The glucose transporter-1(Glut-1),a key ratelimiting factor in the transport and metabolism of glucose in cancer cells,is over-expressed in many human cancer cells and this overexpression is correlated with poor biological behavior. The increased levels of Glut-1 expression in hepatocellular carcinoma(HCC)cells functionally affect tumorigenicity.This study was undertaken to investigate effects of suppressing Glut-1 by an antisense oligodeoxynucleotide(AS-ODN)on the growth of human hepatocellular carcinoma(HepG-2)cells. METHODS:We used AS-ODN targeting against the Glut-1 gene in a HepG-2 cell line.There were four experimental groups: empty pcDNA3.1 vector(mock transfection),pcDNA3.1-anti-Glut(+),pcDNA3.1-Glut(+),and non-transfected HepG-2 cells. The Glut-1 mRNA expression was detected by RT-PCR and the Glut-1 protein expression by Western blotting after cell culture, and the glucose uptake was detected after glucose stimulation in each group. RESULTS:Compared with non-transfected HepG-2 or Glut-1 pcDNA3.1,a down-regulation of Glut-1 mRNA in HepG-2 cells transfected with anti-Glut-1 pcDNA3.1 was noted(P<0.05).Glut-1 protein in HepG-2 cells transfected with Glut-1 AS-ODN was decreased compared with non-transfected HepG-2,Glut-1 pcDNA3.1,or empty vectors. Glucose uptake by the HepG-2 cells transfected with AS-ODN was decreased at 1 hour after glucose stimulation.CONCLUSIONS:The application of Glut-1 AS-ODN can down-regulate the expression of Glut-1 at mRNA and protein,and inhibit glucose uptake partially in HepG-2 cells.The Glut-1 gene maybe a potential therapeutic target for HCC.展开更多
A novel tungstosilicic polyoxometalate containing 5-fluorouracil and Nd, K26(C4H4FN2O2)8Nd(SiW11O39)4·5H2O (FNSW) was synthesized and its structure was characterized by using elemental analysis, FT-IR spectra, X-...A novel tungstosilicic polyoxometalate containing 5-fluorouracil and Nd, K26(C4H4FN2O2)8Nd(SiW11O39)4·5H2O (FNSW) was synthesized and its structure was characterized by using elemental analysis, FT-IR spectra, X-ray powder diffraction, UV-vis spectra and TG. The results indicated that the compound FNSW had Keggin structure of heteropolyanion and ring structure of 5-fluorouracil, and it had a good thermal stability. With 5-fluorouracil for the positive control group, the cytotoxicity tests in human renal embryonic cell HEK293 and the antitumor activity tests in hepatocellular carcinoma cell HepG-2 were carried out by the methyl thiazolyl tetrazolium method. The toxicity of the compound FNSW was lower than that of 5-fluorouracil, and compared with 5-fluorouracil the compound FNSW could inhibit HepG-2 cell in vitro with significant difference. The rare earth element Nd increased the biological activity of polyoxometalate significantly.展开更多
Two novel rare earth substituted phosphotungstates containing 5-fluorouracil,K 9（C 4 H 4 FN 2 O 2） 2 Nd（PW 11 O 39） 2 ·25H 2 O（FNdPW） and K 9（C 4 H 4 FN 2 O 2） 2 Ce（PW 11 O 39） 2 ·23H 2 O（FCePW）,...Two novel rare earth substituted phosphotungstates containing 5-fluorouracil,K 9（C 4 H 4 FN 2 O 2） 2 Nd（PW 11 O 39） 2 ·25H 2 O（FNdPW） and K 9（C 4 H 4 FN 2 O 2） 2 Ce（PW 11 O 39） 2 ·23H 2 O（FCePW）,were synthesized and characterized by elementary analysis,FT-IR spectra,X-ray powder diffraction and 1 H NMR.The thermal analysis showed that FNdPW decomposed at 210 and 493 oC,and FCePW decomposed at 223 and 471 oC,both of which had good thermal stabilities.MTT tests were performed to study the antitumor activities against HeLa cells and HepG-2 cells of FNdPW,FCePW,5-fluorouracil,C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 ·8H 2 O and K 11 Ln（PW 11 O 39） 2 ·xH 2 O（Ln=Nd,Ce）,and their cytotoxicities against HEK 293 cells.The results showed that FNdPW and FCePW possessed higher antitumor activities and lower cytotoxicities than those of 5-fluorouracil and C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 ·8H 2 O,of which FNdPW exhibited the highest antitumor activates against HeLa cells（EC 50 =3.41×10-6 mol/L） and HepG-2 cells（EC 50 =6.24×10-6 mol/L）.Thus the introduction of rare earth elements and 5-fluorouracil could significantly enhance antitumor effect of polyoxometalates.展开更多
Two rare earth substituted Keggin-type phosphomngstates containing 5-fluorouracil, K10C4H4FN2O2Y（PW11O39）2· 10H2O （FYPW） and Kg（C4H4FN2O2）2La（PWl1O39）2· 18H2O （FLaPW） were synthesized in aqueous so...Two rare earth substituted Keggin-type phosphomngstates containing 5-fluorouracil, K10C4H4FN2O2Y（PW11O39）2· 10H2O （FYPW） and Kg（C4H4FN2O2）2La（PWl1O39）2· 18H2O （FLaPW） were synthesized in aqueous solution, and the structures were characterized by Fourier transform infrared spectroscopy （FT-IR）, element analysis, inductively coupled plasma spectrometry （ICP）, X-ray powder diffraction （XRD） and 1H nuclear magnetic resonance （NMR）. Thermal analysis showed that the decomposition processes of the two compounds could be di- vided into three steps, the loss of crystal water, the decomposition of 5-fluorouracil unit and the decomposition of Keggin-type polyanions. The in vitro cytotoxicities against HEK 293, HeLa and HepG-2 cells were studied by methyl thiazolyl tetrazolium （MTT） assay. The results showed that FYPW and FLaPW had higher antitumor activities than 5-fluorouracil, C4H4FN2O2H2PW12O40.8H2O and rare earth substituted polyoxometalates KllLn（PW11O39）2@nH2O （Ln-Y, La）. It was concluded that introducing 5-fluorouracil and rare earth （Y or La） into its structure was a considerable way to enhance antitumor activities ofpolyoxometalates.展开更多
目的研究人重组内皮抑素(recombinant human endostatin)(简称内皮抑素)对人肝癌单独及联合化疗的作用。方法在体外单独应用内皮抑素或者联合细胞周期特异性化疗药物氟尿嘧啶(flur-ouracil,5-Fu)作用于HepG-2细胞,用cck-8检测及流式细...目的研究人重组内皮抑素(recombinant human endostatin)(简称内皮抑素)对人肝癌单独及联合化疗的作用。方法在体外单独应用内皮抑素或者联合细胞周期特异性化疗药物氟尿嘧啶(flur-ouracil,5-Fu)作用于HepG-2细胞,用cck-8检测及流式细胞技术研究内皮抑素对HepG-2作用。结果 cck-8检验结果显示药物作用24 h,单独内皮抑素仅在100μg/mL的剂量时对HepG-2细胞在体外有轻度杀伤作用,细胞死亡率为20.7%,在其余浓度无明显杀伤作用;作用48 h,内皮抑素在50μg/mL、100μg/mL、200μg/mL对HepG-2均有一定杀伤作用,细胞死亡率分别为20.8%、46.3%、15.8%;在各时间段和浓度的内皮抑素对HepG-2杀伤作用显著小于相应内皮抑素+5-Fu组(P<0.05);流式细胞技术检验100μg/mL浓度内皮抑素诱导HepG-2凋亡的作用;内皮抑素100μg/mL在48 h对人脐静脉内皮细胞有诱导凋亡作用,凋亡率为19.5%(对照组为11.7%)。结论内皮抑素对人肝癌HepG-2细胞有一定的杀伤作用,但并非在所有浓度和作用时段对人肝癌HepG-2细胞及脐静脉内皮细胞有凋亡诱导作用。展开更多
文摘BACKGROUND:The glucose transporter-1(Glut-1),a key ratelimiting factor in the transport and metabolism of glucose in cancer cells,is over-expressed in many human cancer cells and this overexpression is correlated with poor biological behavior. The increased levels of Glut-1 expression in hepatocellular carcinoma(HCC)cells functionally affect tumorigenicity.This study was undertaken to investigate effects of suppressing Glut-1 by an antisense oligodeoxynucleotide(AS-ODN)on the growth of human hepatocellular carcinoma(HepG-2)cells. METHODS:We used AS-ODN targeting against the Glut-1 gene in a HepG-2 cell line.There were four experimental groups: empty pcDNA3.1 vector(mock transfection),pcDNA3.1-anti-Glut(+),pcDNA3.1-Glut(+),and non-transfected HepG-2 cells. The Glut-1 mRNA expression was detected by RT-PCR and the Glut-1 protein expression by Western blotting after cell culture, and the glucose uptake was detected after glucose stimulation in each group. RESULTS:Compared with non-transfected HepG-2 or Glut-1 pcDNA3.1,a down-regulation of Glut-1 mRNA in HepG-2 cells transfected with anti-Glut-1 pcDNA3.1 was noted(P<0.05).Glut-1 protein in HepG-2 cells transfected with Glut-1 AS-ODN was decreased compared with non-transfected HepG-2,Glut-1 pcDNA3.1,or empty vectors. Glucose uptake by the HepG-2 cells transfected with AS-ODN was decreased at 1 hour after glucose stimulation.CONCLUSIONS:The application of Glut-1 AS-ODN can down-regulate the expression of Glut-1 at mRNA and protein,and inhibit glucose uptake partially in HepG-2 cells.The Glut-1 gene maybe a potential therapeutic target for HCC.
基金Project supported by the Chemical Materials Institute, China Academy of Engineering Physicsthe Doctoral Innovation Research Assistance Program of the Science and Technology Review
文摘A novel tungstosilicic polyoxometalate containing 5-fluorouracil and Nd, K26(C4H4FN2O2)8Nd(SiW11O39)4·5H2O (FNSW) was synthesized and its structure was characterized by using elemental analysis, FT-IR spectra, X-ray powder diffraction, UV-vis spectra and TG. The results indicated that the compound FNSW had Keggin structure of heteropolyanion and ring structure of 5-fluorouracil, and it had a good thermal stability. With 5-fluorouracil for the positive control group, the cytotoxicity tests in human renal embryonic cell HEK293 and the antitumor activity tests in hepatocellular carcinoma cell HepG-2 were carried out by the methyl thiazolyl tetrazolium method. The toxicity of the compound FNSW was lower than that of 5-fluorouracil, and compared with 5-fluorouracil the compound FNSW could inhibit HepG-2 cell in vitro with significant difference. The rare earth element Nd increased the biological activity of polyoxometalate significantly.
基金supported by Doctoral Innovation Research Assistance Program of the Science and Technology Review (kjdb200902-11)
文摘Two novel rare earth substituted phosphotungstates containing 5-fluorouracil,K 9（C 4 H 4 FN 2 O 2） 2 Nd（PW 11 O 39） 2 ·25H 2 O（FNdPW） and K 9（C 4 H 4 FN 2 O 2） 2 Ce（PW 11 O 39） 2 ·23H 2 O（FCePW）,were synthesized and characterized by elementary analysis,FT-IR spectra,X-ray powder diffraction and 1 H NMR.The thermal analysis showed that FNdPW decomposed at 210 and 493 oC,and FCePW decomposed at 223 and 471 oC,both of which had good thermal stabilities.MTT tests were performed to study the antitumor activities against HeLa cells and HepG-2 cells of FNdPW,FCePW,5-fluorouracil,C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 ·8H 2 O and K 11 Ln（PW 11 O 39） 2 ·xH 2 O（Ln=Nd,Ce）,and their cytotoxicities against HEK 293 cells.The results showed that FNdPW and FCePW possessed higher antitumor activities and lower cytotoxicities than those of 5-fluorouracil and C 4 H 4 FN 2 O 2 H 2 PW 12 O 40 ·8H 2 O,of which FNdPW exhibited the highest antitumor activates against HeLa cells（EC 50 =3.41×10-6 mol/L） and HepG-2 cells（EC 50 =6.24×10-6 mol/L）.Thus the introduction of rare earth elements and 5-fluorouracil could significantly enhance antitumor effect of polyoxometalates.
基金Project supported by Institution of Chemical Materials,China Academy of Engineering Physics
文摘Two rare earth substituted Keggin-type phosphomngstates containing 5-fluorouracil, K10C4H4FN2O2Y（PW11O39）2· 10H2O （FYPW） and Kg（C4H4FN2O2）2La（PWl1O39）2· 18H2O （FLaPW） were synthesized in aqueous solution, and the structures were characterized by Fourier transform infrared spectroscopy （FT-IR）, element analysis, inductively coupled plasma spectrometry （ICP）, X-ray powder diffraction （XRD） and 1H nuclear magnetic resonance （NMR）. Thermal analysis showed that the decomposition processes of the two compounds could be di- vided into three steps, the loss of crystal water, the decomposition of 5-fluorouracil unit and the decomposition of Keggin-type polyanions. The in vitro cytotoxicities against HEK 293, HeLa and HepG-2 cells were studied by methyl thiazolyl tetrazolium （MTT） assay. The results showed that FYPW and FLaPW had higher antitumor activities than 5-fluorouracil, C4H4FN2O2H2PW12O40.8H2O and rare earth substituted polyoxometalates KllLn（PW11O39）2@nH2O （Ln-Y, La）. It was concluded that introducing 5-fluorouracil and rare earth （Y or La） into its structure was a considerable way to enhance antitumor activities ofpolyoxometalates.
