1.A preliminary study of AS1411 mediated STAT3 antisense oligonucleotide targeting tumor cells
Baoxiu LIU ; Jiansheng HUANG ; Naishuo ZHU
Fudan University Journal of Medical Sciences 2017;44(4):422-429
Objective To observe the effect of AS1411-mediated signal transduction and activator of transcription 3 (STAT3) antisense oligonucleotide (ASO) targeting tumor cells.Methods RNA was used as coupling molecules to link the targeting molecules AS1411 and effector molecules ASO.Prediction and analysis of the secondary structure of the pre-synthesis of chimeric molecules by RNA Structure software.Agarose gel electrophoresis was used to test the stability of chimeric molecules in serum and cell lysis solution.Using flow cytometry and confocal fluorescence microscope were used to estimate the internalization of AS1411-mediated STAT3 ASO.Inhibitory effect of ASO on the growth of tumor cells was detected by CCK-8 kit.RT-PCR and Western blot was used to measure the expression levels of tumor related genes.Results STAT3 ASOs mediated by AS1411 can enter tumor cells efficiently to inhibit the transcription and translation of C-myc,Cyclin D1,Bcl-xl and PD-L1 gene,and also can inhibit the growth of Du145 cells.Conclusions AS1411-mediated STAT3 ASO can enter tumor cells and act as anti-tumor medicine.
2.Aberrant expression of mammalian target of rapamycin in stage ⅢB colon cancer and its significance
Baoxiu LI ; Chunyan LI ; Guolong LIU ; Xiaoshi ZHANG
Medical Journal of Chinese People's Liberation Army 2001;0(08):-
Objective To explore the aberrant expressions of mammalian target of rapamycin (mTOR) and its activation form,pmTOR,in stage IIIB human colon cancer,and analyze the association of mTOR and pmTOR with clinicopathologic characteristics and patients' prognosis. Methods A total of 104 patients with stage IIIB (T 3-4 N1M0) colon cancer with available follow-up data were enrolled. The specimens of colon cancer and clinical data were acquired from these subjects. The expressions of mTOR and pmTOR in tumor tissues and matched normal tissues were detected with immunohistochemistry. The relationship and its significance between the expressions of mTOR and pmTOR and some clinicopathological features,such as gender,age,location of primary tumor,pathological stage and TNM stage,were analyzed. Results The mTOR and pmTOR were found to be expressed in cell membrane and cytoplasm of tumor tissues. Out of the total 104 specimens,positive rate of mTOR and pmTOR accounted for 75.9% (79/104) and 76.9% (80/104),respectively. No significant correlation was noted between the expressions of mTOR and pmTOR and the clinicopathological features by partial correlation analysis. Both univariate analysis and multivariate analysis showed that the expressions of mTOR and pmTOR threw no significant influence on the 5-year overall survival of patients. Nevertheless,subgroup analysis suggested that a high expression of pmTOR along tumor border was likely to contribute to higher risk of death in patients. Conclusion Aberrant expressions of mTOR and pmTOR are noted in patients with locally advanced colon cancer. High expression of pmTOR along the border of tumor tissue may suggest the possibility of invasion and metastasis.
3.Relationship between angiopoietin-2, vascular endothelial growth factor, carbohydrate antigen 199 and carcinoembryonic antigen in the diagnosis and postoperative recurrence and metastasis in colon cancer
Haibo MAO ; Guodong ZHU ; Runya FANG ; Baoxiu LI ; Xisheng FANG ; Guolong LIU
The Journal of Practical Medicine 2019;35(3):428-432
Objective To investigate the diagnosis of colon cancer patients and the prediction of postoperative recurrence and metastasis in patients with colon cancer by serum angiopoietin-2 (Ang-2) , vascular endothelial growth factor (VEGF) , carbohydrate antigen 199 and carcinoembryonic antigen CEA. Methods 100 patients with colon cancer, 100 patients with benign colonic lesions and 100 healthy subjects were examined. The levels of Ang-2, VEGF, CA19-9 and CEA in serum were detected, and the diagnosis and postoperative recurrence and metastasis of colon cancer were investigated. Results The levels of serum Ang-2, VEGF, CA19-9 and CEA in colon cancer group were higher than those in benign lesions and healthy controls (P < 0.05). The levels of Ang-2, VEGF, CA19-9 and CEA were detected. The sensitivity and specificity of each index were significantly higher in the diagnosis of colon cancer. The preoperative recurrence and metastasis rates of patients with positive Ang-2, VEGF, CA19-9 and CEA were higher than those of the negative patients respectively. Survival analysis showed a statistically significant difference in the time of distant metastasis between different expression states (P < 0.05). Conclusion The detection of serum levels of Ang-2, VEGF, CA19-9 and CEA has clinical significance for the diagnosis of colon cancer. Combined detection can improve the diagnostic efficiency; the levels of Ang-2, VEGF, CA19-9 and CEA in serum before surgery colon cancer is associated with recurrence and metastasis, and combined testing can help to assess tumor metastasis.
4.Anti-depressant effect and mechanism of Peiyuan Jieyu Fang (Tonifying-original Qi Releasing-depression Formula) in several mouse models of depression
Baoxiu LIU ; Pingping WANG ; Tao YANG ; Lina LI ; Jianzhi LI ; Hongsheng CHANG
Journal of Beijing University of Traditional Chinese Medicine 2017;40(9):736-742
Objective To study the anti-depressant effect and mechanism of Peiyuan Jieyu Fang (Tonifying-original Qi Releasing-depression Formula).Methods The reserpine depression model was established by intraperitoneal injection of reserpine (2.5 mg/kg) in mice,acute stress depression model,by forced swimming test (FST) in mice,and chronic stress depression model,by long-term bandage (14 d) and noise in mice.The influences of Peiyuan Jieyu Fang on body temperature,ptosis and rate of overstepping bound in reserpine depression model,and on immobility time of FST in acute stress depression model and chronic stress depression model were observed.The content of brain 5-hydroxytryptamine (5-HT),noradrenalin (NA) and indoleamine-2,3-dioxygenase (IDO) in acute stress depression model,and content of 5-HT and IDO in chronic stress depression model were detected by using enzyme-linked immunosorbent assay (ELISA).The expression of IDO mRNA was detected by using fluorescence quantitative polymerase chain reaction (PCR) in chronic stress depression model.Results The decrease of body temperature was antagonized in all Peiyuan Jieyu Fang groups (abbreviated as high-dose group,mid-dose group and low-dose group) in reserpine depression model (P < 0.01).The ptosis and akinesia induced by reserpine were relieved in high-dose group (P < 0.05),and akinesia was relieved in low-dose group (P < 0.05).The immobility time of FST was shortened (P < 0.05,P < 0.01),and content of 5-HT and NA were significantly increased in acute stress depression model in mid-dose group and low-dose group (P <0.05,P <0.01).The immobility time of FST was shortened in varying degrees,content of 5-HT was increased,content of IDO was decreased and IDO mRNA expression was up-regulated in chronic stress depression model in high-dose group,mid-dose group and low-dose group (P < 0.05).Conclusion Peiyuan Jieyu Fang has some relief effects on depression symptoms induced by reserpine,FST and chronic stress in mice.The mechanism may be related to that Peiyuan Jieyu Fang can increase the content of 5-HT and NA,inhibit IDO activity,and down-regulate IDO mRNA expression.
5.Effects of Peiyuan Jieyu Formula on TRP-KYN metabolic pathway and its neuron protection mechanism in depressed rats induced by glucocorti-coid
Haina LI ; Lina LI ; Shuyan WANG ; Angran FAN ; Xue YU ; Pingping WANG ; Baoxiu LIU ; Hongsheng CHANG
Journal of Beijing University of Traditional Chinese Medicine 2017;40(12):1011-1017
Objective To study the effects of Peiyuan Jieyu Formula ( PYJYF) on rats treated with glu-cocorticoid, its influences on metabolism of the TRP-KYN pathway and the impacts on hippocampal and cortical neuronal plasticity. Methods 70 rats were randomly divided into the following 7 groups ( n=10 in each group): normal blank group, model group, fluoxetine group, mid- and high-dose Tiansi Yin ( TSY) groups, Sini San ( SNS) groups, and PYJYF groups. Rat model of depression was established by intraperitoneal injection of glucocorticoid for 28 days. Sucrose solution consumption and Open-field test were conducted. The content of TRP, KYN, KA and Q in serum was measuredby using HPLC-MS/MS technique. The mRNA expressions of NR and BDNF in brain tissue were measured by using RT-PCR. Results 28 days after the injection of glucocorticoid in model group, the consumption of sucrose solution and total score in open-field test was significantly decreased ( P <0 . 05 ) . The ratios of KYN/TRP and KYN/KA increased significantly ( P<0 . 05 ) . The mRNA expression level of BDNF in hippocampal de-creased significantly ( P<0 . 05 ) . The mRNA expression level of NR increased significantly ( P<0 . 05 ) . Peiyuan Jieyu Formula increased the consumption of sucrose solution (P<0. 05),the total score in open-field test,the ratios of KYN/Q and the mRNA expression level of BDNF in hippocampus(P<0. 05) when compared with the model group. The ratios of KYN/TRP and KYN/KA(P<0. 05) and the mRNA ex-pression level of NR in cortex ( P <0. 05 ) of Peiyuan Jieyu Formula group decreased. Conclusion Peiyuan Jieyu Formula can reduce the metabolism of TRP-KYN, inhibit neurotoxicity, improve neural protection, and promote the hippocampal and cortical neural plasticity.