ABSTRACT
Objective:To investigate the effects of ribonucleic acid for injection Ⅱ, often called RNA Ⅱ for short, combined with chemotherapeutic drug cyclophosphamide (CTX) on the tumor inhibition and survival of sarcoma cell S180 tumor-bearing mice.Methods:The solid transplanted tumor mouse model of sarcoma cell S180 and peritoneal fluid tumor mouse model were established respectively. CTX (25 mg/kg, once for 2 days) alone or combined with low-dose (25 mg/kg, once a day) and medium-dose (50 mg/kg, once a day) RNA Ⅱ were injected intraperitoneally into solid transplanted tumor mice for 10 d. CTX (25 mg/kg, once for 2 days) alone, medium-dose (50 mg/kg, once a day) or high-dose (100 mg/kg, once a day) RNA Ⅱ alone or combined with CTX were injected intraperitoneally into peritoneal effusion tumor mice until all mice died. The two models were set up for modeling groups without drug treatment, 8 mice in each group. The body mass of solid transplanted tumor mice after administration was weighed, the tumor tissue in vivo was taken out and weighed after the mice were executed, and the tumor inhibition rate was calculated. The body mass of peritoneal effusion tumor mice after administration was weighed, the growth rate of body mass was calculated, the survival curve of each group was drawn, and the life extension rate was calculated.Results:(1) Solid transplanted tumor mice: the body mass of mice in each administration group was lower than that in the modeling group after administration. During the administration period, the tumor volume in the modeling group was much higher than that in each administration group. From the 8th day of administration, the tumor volume in vivo in the CTX group began to be larger compared with that in the two combined administration groups. After stopping the administration and killing the mice, the weighing showed that the tumor mass of each administration group was lower than that in the modeling group (all P < 0.01), the tumor mass of CTX + RNA Ⅱ low-dose group and CTX + RNA Ⅱ medium-dose group was lower than that of CTX group (all P < 0.05), and the tumor inhibition rate of the two groups was higher than that of CTX group (83.6%, 77.2% vs. 58.5%). (2) Peritoneal effusion tumor mice: after administration for 12 d, the body mass growth rate of mice in CTX group was increased rapidly and reached the highest, and the body mass growth rate of mice in the two combined administration groups was lower than that in other groups. The life prolongation rates of RNA Ⅱ high-dose group and CTX group were 48.2% and 53.2% respectively, which had the same effect on life prolongation. The life prolongation rate in RNA Ⅱ medium-dose group was 20.9%. The life prolongation rates of CTX + RNA Ⅱ medium-dose group and CTX + RNA Ⅱ high-dose group were 94.2% and 105.0% respectively. Conclusions:RNA Ⅱ combined with CTX can significantly prolong the survival time of sarcoma cell S180 tumor-bearing mice, increase the tumor inhibition rate and improve the quality of life of the mice. Both of them have a synergistic effect.
ABSTRACT
Aim To evaluate the mucosal-protective effects of carboxymethylpachyman( CMP) on Fluorou-racil(5-Fu)-induced mice intestinal mucositis and ex-plore its mechanisms. Methods ICR mice were as-signed randomly to four groups:normal group( n=8;re-ceiving pure water orally for 14 d) ,CMP group( n=8;200 mg·kg-1 CMP for 14 d orally),5-Fu group(n=8;25 mg·kg-1 5-Fu for 7 d,intraperitoneally( i. p. ) , and CMP+5-Fu group( n=8;200 mg·kg-1 CMP for 14 d orally and 25 mg·kg-1 5-Fu for 7 d,i. p. ). At day 14the mice were sacrificed. The intestinal propel-ling rate and the colon length were measured. ROS, GSH and IL-1βcontents,and CAT,GSH-Px activities in homogenate supernatant of PPs were measured by kits for observing the effects of CMP on mice lipid peroxida-tion and intestinal mucosal inflammatory induced by 5-Fu. Colon tissues were used for hematoxylin and eosin ( HE ) staining for the determination of the effect of CMP on mice colon histopathology, immunohistochem-istry for the protein levels of NF-κB and p-p38 . Results CMP significantly extended colon lengths,accelerate the intestinal propelling rates, reduced colonic mucosa epithelium goblet cell loss, inflammatory cells infiltra-tion,and crypt depth shallow induced by 5-Fu. CMP obviously reduced ROS and IL-1β contents, and pre-vented reductions in homogenate supernatant of PPs GSH content, CATand GSH-Px activities by 5-Fu ad-ministration,and also reduced the expression of NF-κB and p-p38 in colon tissues. However, CMP alone had no effect on the colon of normal mice. Conclusion The current study demonstrates that CMP may have sig-nificant protective effects against 5-Fu-induced intesti-nal mucositis. Its mechanism may be related to enhan-cing the antioxidant activity,anti-inflammatory and an-ti-apoptotic effects.
ABSTRACT
Aim Toinvestigatetheeffectsoftriptonot-erpene methyl ether ( TME ) , a diterpene derived from the medicinal plant Triptergium wilfordii, on human gastric cancer AGS cell proliferation inhibition and ap-optosisinducedinvitro.Methods MTTassaywas used for screening tumor spectrum and detecting the vi-ability of AGS cells and normal human gastric epitheli-al cells GES-1 . Cell morphology was observed by light microscopy and AO / EB staining. Flow cytometry was used to detect cell apoptotic rate and cell cycle. JC-1 staining and fluorescence probe DCFH-DA were em-ployed to detect the changes of mitochondrial mem-brane potential and reactive oxygen species ( ROS ) . The effect of inhibiting AGS clonogenic survival was as-sayed by the method of plate clone formation. Western blot was used to analyse the expression of caspase-3 , caspase-8,Bcl-2andBax.Results MTTresults showed that TME exhibited significantly higher cytotox-icity to gastric cancer AGS cell line than to noncancer-ous cell line GES-1. IC50 for AGS of 48 h treatment was 23 . 85 μmol · L-1 . TME significantly inhibited colony formation and caused morphological changes in AGS cells. Annexin V-FITC / PI double staining showed the apoptotic rate increased. DCFH-DA stai-ning showed TME resulted in an increase in intracellu-lar ROS levels. Mitochondrial membrane potential de-creased after TME treatment. Western blot results showed that TME increased the proportion of Bax /Bcl-2 , with the activation of caspase-8 and caspase-3 . The broad-spectrum caspase inhibitor z-VAD-fmk pre-treatment reduced the expression of caspase-8 and caspase-3. TME enabled AGS cell cycle arrest in G0/G1phase.Conclusion TMEpossessespotenttumor selected toxicity and can induce apoptosis of AGS cells through cell cycle arrest, which is associated with Bcl-2 protein family.