ABSTRACT
Objective To explore the effects of graphene oxide (GO)-polyethylene glycol (PEG)-folic acid (FA)-pyrenemethylamine hydrochloride (PyNH2)-mediated RNA interference (RNAi) of hypoxia-inducible factor-1α (HIF-1α) on the biological behaviors of human pancreatic cancer Patu8988 cells.Methods GO-PEG-FA-PyNH2 and RNAi targeting HIF-1α gene (GO-PEG-FA-PyNH2-HIF-1α-RNAi)was constructed.The expressions of HIF-1α and glucose transporter 1 (Glut-l) in Patu8988 cells were determined after knockdown of HIF-1α by RNAi.The invasive ability,the proliferation and the cell cycle of Patu8988 cells were investigated.The effect of HIF-1α knockdown on the uptake of 18F-fluorodeoxyglucose (FDG) in Patu8988 cells was also detected.Comparison of data was conducted by one-way analysis of variance and least significant difference t test.Results The GO-PEG-FA-PyNH2 was successfully constructed,and no cytotoxicity was found.Under the hypoxia or normoxia state,the mRNA and protein levels of HIF-1α and mRNA level of Glut-1 in cells transfected with GO-PEG-FA-PyNH2-HIF-1α-RNAi (study group) were lower than those in cells transfected with GO-PEG-FA-PyNH2 (negative group) and cells transfected with Opti-minimal essential medium (Opti-MEM,control group;F=30.25-32.58,t=3.66-5.81,all P＜0.05);the numbers of migrated cells in the study group were much lower than those in the negative group and the control group (F=38.63 and 41.35,t=20.51-35.25,all P＜0.01);the cell proliferation in the study group was significantly lower than that in the negative group and the control group (F=35.19 and 38.11,t =15.11-22.19,all P＜0.05).The proportions of G0/G1 cells in the study group were higher than those in the negative group and the control group (F=34.60 and 34.83,t=11.55-34.56,all P＜0.05);the 18 F-FDG uptake in the study group was lower than that in the negative group and control group (F=29.85 and 31.69,t =3.35-4.35,all P＜0.05).Conclusion GO-PEG-FA-PyNH2-mediated HIF-1α RNAi inhibits the expression of HIF-1α in pancreatic cancer cells,leading to changes in related biological behaviors.
ABSTRACT
Objective To evaluate the significance of tumor markers CEA and CA15-3,and biochemical markers of bone turnover (total procol]agen type Ⅰ amino-terminal propeptide (TP I NP),β-isomerized carboxyterminal propeptide (β-CTx),ALP and PTH) in the diagnosis of bone metastasis from breast cancer.Methods A total of 78 patients (all females) with mean age (56.72 ± 10.76) years,who were diagnosed with breast cancer,were included in this study.The patients were divided into two groups based on radionuclide bone imaging:with bone metastasis (n =32) and without bone metastasis (n =46).The serum concentrations of CEA,CA15-3,TP I NP,[β-CTx,PTH,ALP were measured.Gleason scores were evaluated.The diagnostic value was evaluated by ROC curve.The two groups were compared using two-sample t test.The correlations between bone metastasis and tumor markers,bone metastasis and biochemical markers of bone turnover were analyzed with Pearson correlation and logistic analysis.Results The serum levels of CEA,CA15-3,TPINP,β-CTx,PTH and ALP were significantly higher in the group with bone metastasis than those in the group without bone metastasis (t:4.16-7.56,all P ＜ 0.05).For the diagnosis of bone metastasis from breast cancer,the AUC of CEA,CA15-3,TPINP,[β-CTx,PTH and ALP was 0.815,0.887,0.869,0.852,0.844,0.731,respectively.Using the cut-off values of 4.18 μg/L for CEA,0.04 U/L for CA15-3,49.70 μg/L for TP I NP,0.47 pg/L for β-CTx,54.90 ng/L for PTH and 49.90 U/L for ALP,the sensitivities were 56.3％ (18/32),75.0％ (24/32),78.1％ (25/32),81.3％ (26/32),78.1％ (25/32),68.8％ (22/32) and the specificities were 80.4％ (37/46),84.8％ (39/46),76.1％ (35/46),78.3％ (36/46),69.6％ (32/46),58.7％ (27/46),respectively.CEA,CA15-3,TPINP,β-CTx,PTH,ALP and Gleason score were positively correlated with the presence of bone metastasis (r:0.267-0.636,all P ＜ 0.05).CEA,CA15-3,TP I NP,β-CTx,PTH and Gleason score were independent predictors for bone metastasis of breast cancer (odds ratios:2.45,3.44,1.24,1.54,1.11,2.22,all P ＜0.05).The total coincidence rate of regression model was 81.3％ (26/32) in patients with bone metastasis.Conclusions The diagnostic values of CEA,CA15-3,TP I NP,β-CTx and PTH are comparable.Combined use of these parameters may be helpful for the early diagnosis of bone metastasis from breast cancer.