1.FGF2 confers chemo-resistance of breast cancer cells by activating Akt-mTOR signal
Yixue GU ; Xiaoting JIA ; Liyun LUO ; Guopei ZHENG ; Zhimin HE
The Journal of Practical Medicine 2017;33(1):36-40
] Objective To explore the role and mechanisms of FGF2 in chemo?resistance in breast cancer. Methods The inhibitors for different signal pathway were used to treat two drug?resistant breast cancer cell lines MCF?7/5?Fu and T47D/5?Fu established in our lab. MTS assay was used to determine chemo?sensitivity and Hoechst stain was used to measure apoptosis. Protein activation and FGF2 protein level in cell culture medium were detected by western blot and ELISA respectively. Results Akt inhibitor MK?2206 (20 nM) and mTOR inhibitor AZD8055 (2 nM) significantly reversed the chemo?resistance of MCF?7/5?Fu and T47D/5?Fu cell lines to 5?Fu and paclitaxel, but ERK1/2 inhibitor SCH772984 showed no significant effect. Compared to parent cell lines MCF?7 and T47D, p?Akt and p?S6K (represented as mTORactivity) levels were obviously up?regulated in MCF?7/5?Fu and T47D/5?Fu cell lines, and so do the FGF2 mRNA level and FGF2 protein level from culture medium. Moreover, FGFR inhibitor AZD4547 (4 nM) markedly reversed the chemo?resistance of MCF?7/5?Fu and T47D/5?Fu cell lines to 5?Fu and paclitaxel and down?regulated activation of FGFR?Akt?mTOR signal pathway. In agreement, FGF2 protein (10ng/ml) enhanced the chemo?resistance of MCF?7 and T47D cell lines to 5?Fu and paclitaxel and up?regulated activation of FGFR?Akt?mTOR signal pathway. Conclusion Activation of FGF2?FGFR?Akt?mTOR signal pathway promoted chemo?resistance of breast cancer cells.
2.Effects of vibrating the abdomen on peripheral blood gastrointestinal hormones and gastrointestinal motility of young anorexia model rats
Ling ZHOU ; Yan ZHANG ; Nan GU ; Weijie BAI ; Liyun YANG ; Jinlong LI ; Yanping YANG
Journal of Acupuncture and Tuina Science 2024;22(2):104-110
Objective:To observe the therapeutic effect of vibrating the abdomen on anorexia model rats,as well as its effects on cholecystokinin octapeptide(CCK-8)and motilin(MTL)in the peripheral blood. Methods:Forty young rats were randomly divided into a normal group(n=10)and a modeling group(n=30).Rats in the normal group were fed common feed.The anorexia model was established by the etiological simulation method in the modeling group,and these rats were further randomly divided into a drug group,a vibrating abdomen group,and a model group 3 weeks after the anorexia model was induced,with 10 rats in each group.The drug group was given Jian Wei Xiao Shi Pian by intragastric administration at a dose of 0.72 g/(kg·bw)(0.72 g drug was dissolved in 10 mL purified water).The normal group and the model group were given purified water once a day in the morning.The vibrating abdomen group was treated with vibrating the abdomen once a day for 21 times.The body mass,food intake,serum CCK-8,MTL,gastrin(GAS),neurotensin(NT)levels,and the intestinal propulsion rate of rats in each group were measured. Results:Compared with the model group,the body mass,food intake,serum MTL and GAS levels,and the small intestine propulsion rate increased significantly,and the serum CCK-8 and NT levels,the gastric residual rate decreased significantly in the vibrating abdomen group and the drug group(P<0.05).There were no significant differences between the vibrating abdomen group and the drug group(P>0.05). Conclusion:Vibrating the abdomen increases the food intake and body mass of anorexia model rats,reduces the residue of gastric contents,improves the small intestine propulsion rate,and therefore has a good therapeutic effect on anorexia.The mechanism may be related to inhibiting the secretion of CCK-8 and NT in plasma and promoting the release of MTL and GAS in serum.
3.Investigation and Analysis on the Clinical Use of Curcumae Rhizoma in Jiangsu Province Based on Ingredi-ent and Efficacy Difference
Liyun GU ; Shali DU ; Lei ZHANG ; Shen SONG
China Pharmacy 2017;28(28):4019-4022
OBJECTIVE:To provide reference for clinical rational use of curcumae rhizoma. METHODS:According to litera-ture retrieval,the chemical structures,ingredient and efficacy difference of curcumae rhizoma with different sources and difference processed products were summed up. According to literature retrieval,telephone consultation and network retrieval,the production status of products with different sources and difference processing and the application in clinic and preparations in Jiangsu province were analyzed. RESULTS:The volatile oil content was the highest in Curcuma wenyujin;curcumin content was the highest in Cur-cuma phaeocaulis;the contents of 4 main active ingredients(curdione,curcumol,germacrone and curcumin)were relatively lower in Curcuma kwangsiensis,and there were quite different ingredients in the C. kwangsiensis from different producing areas. Results of investigating the annual output of medicinal materials in Sichuan,Guangxi and Zhejiang in 2016 showed,the annual output of C. kwangsiensis was the highest,and C. wenyujin and C. phaeocaulis were relatively lower. In the investigated 14 manufacturers producing curcumae rhizoma oil in China,12 took C. wenyujin and 2 took C. phaeocaulis as raw material. While the 9 manufactur-ers in Jiangxi province mostly took C. wenyujin(locally produced)as raw material,which was not from the genuine producing ar-ea-Zhejiang province. In the 10 third-grade class-A TCM hospitals and 20 retail TCM pharmacies in Jiangsu province,the C. phaeo-caulis and C. kwangsiensis were mainly used,in which,the use proportion of C. kwangsiensis accounted for about 70%,and C. wenyujin used little in clinic. The main processed product in clinic was curcumae rhizoma processed by vinegar,and crude product was rarely used. CONCLUSIONS:Currently,the clinical use of curcumae rhizoma shows problems in narrow selection of pro-cessed products and uneven quality,which can be solved by cultivating fine varieties in producing areas,increasing the planting amount of C. phaeocaulis,drug regulatory authorities'strict rules for processed products of curcumae rhizoma in hospitals and re-tail pharmacies.
4.Influence of Tuina plus oxiracetam on serum inflammatory factors and oxidative stress in mild vascular dementia patients
Nan GU ; Yuexian FAN ; Ling ZHOU ; Yan ZHANG ; Weijie BAI ; Yanfeng LI ; Liyun YANG ; Jinlong LI ; Jue HONG
Journal of Acupuncture and Tuina Science 2022;20(4):273-280
Objective: To observe the clinical efficacy of Tuina (Chinese therapeutic massage) plus oxiracetam in treating mild vascular dementia (VD) and seek its underlying mechanism. Methods: Ninety-six patients with mild VD were randomized into an observation group and a control group, with 47 cases in the observation group and 49 cases in the control group. The control group received oral oxiracetam capsules for treatment, and the observation group was given additional Tuina treatment. Before and after treatment, the mini-mental state examination (MMSE) was adopted to assess the patient's cognitive function; the activities of daily living (ADL) scale was used to evaluate their ability to conduct daily activities; changes in the serum inflammatory factors and oxidative stress indicators were also detected. Results: After treatment, the serum content of malondialdehyde (MDA) decreased in both groups (P<0.05) and was lower in the observation group than in the control group (P<0.05); the serum contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) increased in both groups (P<0.05) and were higher in the observation group than in the control group (P<0.05); the serum contents of interleukin (IL)-1, tumor necrosis factor (TNF)-α, IL-6, and IL-8 declined in both groups (P<0.05) and were lower in the observation group than in the control group (P<0.05). After the intervention, the levels of systolic velocity (Vs) and mean velocity (Vm) of the middle cerebral artery elevated, and the pulsatility index (PI) dropped in patients in the two groups, showing significant intra-group differences (P<0.05); the levels of Vs and Vm in the observation group were higher than those in the control group, and the PI was lower in the observation group than in the control group, showing significant between-group differences (P<0.05). The MMSE and ADL scores increased in both groups after the intervention (P<0.05) and were higher in the observation group than in the control group (P<0.05). Conclusion: In the treatment of mild VD, Tuina plus oxiracetam can improve the cerebral blood supply, ADL, and cognitive function; the mechanism may be associated with the reduction of oxidative stress damages and inflammatory reactions.
5.Evaluation of the metabolism of PEP06,an endostatin-RGDRGD 30-amino-acid polypeptide and a promising novel drug for targeting tumor cells
Liyun NIU ; Huiyu ZHOU ; Yueru LIAN ; Ya GAO ; Yulu LIU ; Ruolan GU ; Zhuona WU ; Xiaoxia ZHU ; Hui GAN ; Zhiyun MENG ; Guifang DOU
Journal of Pharmaceutical Analysis 2022;12(5):766-773
PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.