ABSTRACT
OBJECTIVE： To study the effects of curcumin on gemcitabine （GEM）-resistant pancreatic cancer SW1990 cells and its mechanism. METHODS： CCK8 assay was used to detect the effects of different concentrations of GEM （50， 100， 150， 200， 250 μmol/L） on the survival rate of SW1990 cells and GEM-resistant SW1990 cells （SW1991/GEM resistant cells）； half inhibitory concentration （IC50） and drug resistance multiple were calculated. CCK8 assay was performed to detect the effects of different concentrations of curcumin （1， 5， 10， 20， 40 μmol/L） on survival rate of SW1990/GEM resistant cells， and IC50 was calculated. CCK8 assay was used to detect the effects of curcumin 2.41 μmol/L combined with different concentrations of GEM （25， 50， 75， 100， 125 μmol/L） on the survival rate of SW1990 cells and SW1990/GEM resistant cells， and IC50 and drug resistance reversal fold of GEM were calculated. Flow cytometry was carried out to detect the cell cycle distribution and apoptosis rate of SW1990 after treated with GEM alone or curcumin （2.41 μmol/L） combined with GEM using IC50 of GEM as drug concentration. Western blot assay was used to the protein expression of FAS， AKT， p-AKT， PI3K， p-PI3K， Caspase-3， Bcl-2 and related X protein （Bax）. RT-PCR was used to detect mRNA expression. RESULTS： IC50 of GEM to SW1990 cells was 92 μmol/L. IC50 of GEM to SW1990/GEM resistant cells was 216 μmol/L， and drug resistance multiple SW1990 cells to GEM was 2.35. IC50 of curcumin to SW1990/GEM resistant cells was 9.2 μmol/L. Under 2.41 μmol/L curcumin， IC50 of GEM to SW1990 cells was 75 μmol/L， and IC50 of GEM to SW1990/GEM resistant cells was 98 μmol/L； drug resistance reversal multiple of SW1990/GEM resistant cells to GEM was 2.2. Compared with GEM alone， the apoptosis rate of SW1990 cells and SW1990/GEM resistant cells were increased significantly after curcumin combined with GEM （P＜0.05）， blocking at G0/G1 phase； the protein expression of FAS， p-AKT， p-PI3K and Bcl-2 and mRNA expression of FAS and Bcl-2 were decreased significantly （P＜0.05）； the protein and mRNA expression of Bax and Caspase-3 were increased significantly （P＜0.05）. CONCLUSIONS： Curcumin can reverse drug resistance of SW1990 cells to GEM， the mechanism of which may be associated with PI3K/AKT pathway.
ABSTRACT
Objective To evaluate ketamine-induced cerebral protection in mice with traumatic brain injury (TBI) by magnetic resonance imaging (MRI).Methods Thirty-two pathogen-free healthy male C57BL/6 mice,aged 8 weeks,weighing 26-30 g,were divided into 4 groups using a random number table:control group (group C,n=7),ketanine group (group K,n=7),TBI group (n=9) and TBI plus ketamine group (group TBI+K,n =9).TBI was produced with a pneumatically driven controlled cortical impact device.Ketamine 150 mg/kg was intraperitoneally injected at l h after operation in TBI+K and K groups,while the equal volume of normal saline was given instead in TBI and C groups.Open field test was conducted at 24 h,72 h and 7 days after operation.The animals in TBI and TBI+K groups were scanned by T1-weighted MRI at 6,24 and 72 h after operation,the animals in C and K groups were scanned by MRI at 24 h after operation,and the development of cerebral edema was observed.Results MRI scan showed no cerebral edema in C and K groups,and different degrees of cerebral edema were found in TBI and TBI+K groups.Compared with group C,the locomotor distance was significantly shortened at 24 and 72 h after operation in group TBI (P＜0.05).Compared with group TBI,the size of cerebral edema was significantly decreased,and the locomotor distance was prolonged at 24 and 72 h after operation in group TBI+K (P＜0.05 or 0.01).Conclusion MRI method further clarifies that ketamine can produce cerebral protection to some extent in mice with TBI.