1.FFJ-5 inhibits growth of MCF7 cells and reverses drug resistance of MCF7/DOX cells via down-regulation of PKM2
Tianxiao WANG ; Xiaoli WEI ; Dengyun LI
Chinese Pharmacological Bulletin 2015;(5):721-725,726
Aim To investigate the roles of FFJ-5 in human breast cancer MCF7 cells and drug-resistant MCF7/DOX cells and to explore its mechanisms. Methods MTT assay was used to detect the effect of FFJ-5 on MCF7 and MCF7/DOX cell proliferation and sensitivity of doxorubicin in MCF7/DOX cells.West-ern blot was used to investigate the effect of FFJ-5 on expression of EGFR,p-EGFR,Akt,p-Akt,PKM2, cleaved caspase-3,cleaved PARP and P-gp.DNA lad-der analysis was performed to determine the effect of FFJ-5 on genomic DNA.RT-PCR was performed to de-tect the influence of FFJ-5 on multidrug resistance gene MDR1 mRNA levels.Results The results showed that FFJ-5 inhibited the growth of MCF7 ,inhibited the expression and activity of EGFR and Akt,and conse-quently reduced the expression of PKM2 in MCF7 cells;FFJ-5 activated caspase-3 and induced genomic DNA fragmentation;FFJ-5 also inhibited the growth of MCF7/DOX cells and enhanced the anti-tumor activity of doxorubicin in MCF7/DOX cells.Conclusion The results suggest that FFJ-5 could inhibit MCF7 cell growth and induce MCF7 cell apoptosis through inhibi-tion of EGFR-Akt-PKM2 pathway and activation of ap-optosis-related factors caspase-3 , meanwhile FFJ-5 could also reverse the resistance of MCF7/DOX.
2.A STUDY ON THE ADEQUATE DOSAGE OF VITAMIN E IN PREVENTION AND TREATMENT OF VISCERAL INJURY IN BURNED RATS
Lanxing GAO ; Dengyun XU ; Hong JIN ; Zhongyin WANG ; Zhiqin XU ; Chinfan GU
Acta Nutrimenta Sinica 1956;0(04):-
Forty-two male rats were fed with normal vitamin E( VE)requirement diet, i.e. 0.2mg?100gbw?-1d-1 for one week and then thirty-five rats were induced a 3rd degree burn of 20% BSA, another 7 uninjured rats served as normal contrsol. The burned rats were divided into 5 subgroups receiving VE at the dosage of 0.2, 1, 2, 5,10mg. 100gbw-1?d-1 respectively for 14 days. The re-ults showed that the serum and liver VE contents were lower and the serum LPO higher significantly in the burned rats as compared with the normal control,it wao also found that thymus was atrophic, the thymic cortex become thinner thymocytes constricted, and the splenic corpuscles decreased, the sperm and spermatocytes were markedly decreased with testis atrophy. Whet burned rats were fed VE, as the dosage increased to 2mg?100gbw-1?d-1, the serum and liver VE levels significantly raised and the serum LPO returned to control level. The histological changes of thymus, spleen and testes were nearly similar to the normal control rats.
3.Effects of isoflurane on learning and memory and the expression of GRP78,ATF4 and CHOP in frontal lobe neurons of aged rats
Bei WU ; Gaoya CAO ; Xinsheng WANG ; Dengyun XIA ; Yueping YANG ; Jinliang TENG
Chinese Journal of Behavioral Medicine and Brain Science 2017;26(7):600-604
Objective To observe the changes of learning and memory ability and the expression of GRP8,ATF4 and CHOP in the frontal lobe neurons of rats after isoflurane anesthesia.Methods Male SD aged rats were randomly divided into 4 groups with 15 in each group.Rats in ISO group received 1.5% isoflurane 2 h,SAL group received intraperitoneal injection Salubrinal(1 mg/kg),ISO+SAL group received 1.5% 2 h after intraperitoneal injection Salubrinal(1 mg/kg),C group only inhaled 30% air and oxygen mixture.Morris water maze (MWM) test was performed 24 hours after isoflurane anesthesia,and then the left frontal lobe of rats was collected,gene transcription and protein expression changes of 78-kDa glucose-regulated protein(GRP78),activating transcription factor 4(ATF4),C/EBP homologous protein(CHOP) were evaluated by real-time fluorescence quantitative PCR and immunofluorescence.Results Compared with the C group,the latent time of ISO group was significantly prolonged(ISO group(19.10±2.98)s vs C group (10.54±2.05)s,P<0.05);the number of times passing through the target platform of ISO group was decreased significantly(ISO group (6.78±1.47) vs Cgroup (9.03±1.69),P<0.05);protein expression level of GRP78 was significantly increased in group ISO (ISO group (965.8±86.5) vs C group(247.5±46.3),P<0.05);protein expression level of ATF4 was significantly increased in group ISO(ISO group (470±69.4) vs C group (275.4±56.3),P<0.05) protein expression level of CHOP was significantly increased in group ISO(ISO group (618.7±83.3) vs C group(174.5±71.2),P<0.05).The transcription trends of GRP78,ATF4,CHOP were consistent with their protein expression.Conclusion The decrease of short-term memory ability after isoflurane anesthesia may be related to the activation of endoplasmic reticulum stress pathway in frontal lobe neurons.
4.Protective effect of selective 18 ku translocator protein ligand YL-IPA08 on BV-2 apoptosis induced by corticosterone
Xiangyun JIANG ; Liming ZHANG ; Dengyun XIA ; Shuzheng SUN ; Lei LI ; Yin GUO ; Jie GONG ; Youzhi ZHANG ; Henglin WANG ; Yunfeng LI
Chinese Journal of Pharmacology and Toxicology 2017;31(1):43-50
OBJECTIVE To investigate the protective effect of selective 18 ku translocator protein (TSPO) ligand YL-IPA08 on corticosterone(CORT)-induced apoptosis of BV-2 cells and its potential mecha?nisms. METHODS BV-2 Cells were pretreated with selective TSPO ligand YL-IPA08 1-100 nmol · L-1 and(or) TSPO antagonist PK11195 100 nmol · L-1 for 2 h,and then co-incubated with CORT for another 24 h. The apoptosis rate was measured by flow cytometry. CCK-8 kit was used to test BV-2 cell viability. The protein expression of TSPO was determined by Western blotting. The level of allopreg?nanolone was detected by ELISA kit. RESULTS In line with positive drug-AC-5216, the cell apoptosis rate decreased in YL-IPA08 1-100 nmol · L-1 and CORT co-treatment groups(P<0.01), which was antago?nized by PK11195 100 nmol · L-1 treatment(P<0.05). Cell viability increased in YL-IPA08 100 nmol · L-1and CORT co-treatment groups (P<0.01), which was blocked by PK11195 100 nmol·L-1 treatment(P<0.01). The expression of TSPO and the level of allopregnanolone(P<0.01) were enhanced by YL-IPA08 100 nmol · L-1 pretreatment followed by CORT treatment. The enhancement of allopregnanolone level was blocked by PK11195 100 nmol·L-1 treatment(P<0.05). CONCLUSION YL-IPA08 can protect BV-2 cells from CORT induced apoptosis. The protective effect of YL-IPA08 may be conferred by the increasing level of TSPO expression and allopregnanolone.
5.Investigate the effect of thoracic and abdominal mediastinal drainage tube on the pain and comfort of minimally invasive esophageal cancer patients and nursing care
Jin GUO ; Enshe JIANG ; Yin LI ; Jingru CHEN ; Dengyun WANG ; Dongying LIU
Chinese Journal of Practical Nursing 2018;34(14):1050-1054
Objective Compare the effect of thoracic and abdominal mediastinal tube placement on pain and comfort in patients with minimally invasive esophageal cancer and nursing care. Methods 108 patients with squamous cell carcinoma of the thoracic esophagus were selected from December 2016 to May 2017. The patients were divided into chest group and abdominal group according to the random number comparison table, each with 54 cases. All patients underwent minimally invasive radical resection of esophageal carcinoma. The mediastinum drainage tube was placed at different locations of the chest and abdomen after operation. The duration of intubation, total drainage volume, number of dressing change before and after extubation, degree of pain and comfort after surgery were recorded, drainage tube failure and the incidence of related complication were compared between the two groups. Results There was no significant difference in duration of intubation, total drainage volume, drainage tube failure and the incidence of related complication between Patients with mediastinal tubes placed through the chest and abdomen(P>0.05). The times of dressing change before and after extubation in the abdominal group were (2.8 ± 1.0), (1.9 ± 0.6) times, those in the chest group were (4.5 ± 1.2), (3.6 ± 1.1) times, there were significant difference between the two groups (t=7.841, 9.377, P<0.01). The NRS and VAS score at 1-4 days and extubation in the abdominal group were significantly lower than those in the chest group, the abdominal group were (3.2±1.0), (2.7±0.8), (2.3±0.7), (1.9±0.7), (1.5±0.6) points and (3.7±0.8), (3.4±1.4), (3.0± 0.7), (2.6±1.0), (2.6±1.0) points, the chest group were (3.7±1.3), (3.3±1.1), (2.8±0.8), (2.3±0.8), (2.3±0.7) points and (5.0±0.9), (4.3±1.4), (4.1±1.3), (3.3±1.2), (3.6±1.0) points, there were significant difference between the two groups (t=2.443-7.247, P<0.01 or 0.05). Conclusions Intraoperative abdominal minimally invasive radical mediastinal tube placed esophageal cancer, can significantly relieve pain and improve patient comfort, reduce the frequency of dressing change before and after extubation, not only quickly improve the rehabilitation of patients, but also can avoid the waste of medical resources, it is worthy of clinical promotion.
6.Radiosensitization of sodium glycididazole in esophageal cancer evaluated by 18F-FMISO PET/CT
Dengyun CHEN ; Huiqin XU ; Hui WANG ; Dan ZHANG ; Wenjing YU ; Xiaoyu SU ; Feng QIAO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2019;39(4):218-221
Objective To investigate the feasibility of sodium glycididazole(CMNa)on the radio-sensitization of esophageal cancer(EC)by 18F-fluoromisonidazole(FMISO)PET/CT.Methods A total of 60 patients with EC from December 2016 to December 2017 were enrolled prospectively and were divided into control group(n = 30;21 males,9 females;age:(56.6±10.0)years)and experimental group(n=30;20 males,10 females;age:(59.3±9.0)years)using completely randomized grouping design.Patients in the control group received radiotherapy alone,and those in the experimental group were treated with conventional radiotherapy and CMNa.All patients underwent 18F-FMISO PET/CT imaging 1 week before and after radiotherapy.The imaging results were visually and semi-quantitatively analyzed.The maximum standardized uptake value(SUVmax),tumor/muscle ratio(T/M),and hypoxia volume(HV)were calculated.Paired t test,two-sample t test and/x2 test were used to analyze the data.Results T/M and HV in the control group before and after radiotherapy were 3.92±0.57 vs 1.66±0.35,(1.84±0.31)vs(1.04±0.15)mm3,respectively;T/M and HV in the experimental group before and after radiotherapy were 4.01±0.68 vs 1.27±0.11,(2.01±0.22)vs(0.90±0.09)mm3,respectively.The primary tumor T/M,HV after radiotherapy in 2 groups were significantly lower than those before radiotherapy(t values:12.15-24.43,all P<0.05)and the amplitudes of T/M and HV in the experimental group were significantly higher than those in the control group(?T/M:2.77±0.60vs 2.25±0.49,?HV:(1.12±0.18)vs(0.81±0.26)mm3;t values:3.00 and 1.80,both P<0.05).Meanwhile,the local control rate of EC after 3 months in the experimental group was higher than that in the control group(80.0%(24/30)vs 53.3%(16/30);x2=4.80,P<0.05).Conclusion CMNa has the radiosensitizing effect on EC and the 18F-FMISO PET/CT can evaluate the radiosensitization effect.