ABSTRACT
OBJECTIVE：To study the anti-tumor effect of artemether （ARM）self-microemulsifying drug delivery system （SMEDDS） on human glioma subcutaneously transplanted model mice. METHODS ：Human glioma cell line SHG 44 was inoculated and passed on to establish subcutaneous transplanted tumor model of nude mice. At the 5th，10th，15th，20th and 25th day after inoculation ，the tumor tissue volume was measured and the growth curve was drawn to confirm the initial stage of rapid tumor proliferation. Thirty nude mice was collected to establish subeutaneously transplanted tumor nude model ，and then divided into control group （normal saline ），ARM suspension group [ 60 mg/（kg·d）]，ARM-SMEDDS low-dose ，medium-dose and high-dose groups [ 10，20，30 mg/（kg·d）] at the initial stage of rapid tumor proliferation. They were given normal saline and relevant solution intragastrically once a day ，for consecutive 30 d. The weight change and general sibuation of mice were recorded. The change of tumor volume was determined and relative tumor proliferation rate was calculated. RESULTS ：The subcutaneously transplanted tumor tissue entered the initial stage of rapid tumor proliferation from the 10th day after transplantation. The general situation was normal ，and there was no obvious abnormal reaction in mice of each group during treatment. Since 10th day of administration，tumor tissue volume of mice in ARM-SMEDDS groups were shortened significantly than control group （P＜0.05）. At 15th day of administration ，tumor volume of mice in ARM-SMEDDS groups were shortened significantly than ARM suspension group（P＜0.05）. After last administration ，relative tumor proliferation rates of mice in ARM-SMEDDS groups were decreased significantly，compared with ARM suspension group （P＜0.05）. CONCLUSIONS ：ARM-SMEDDS show significant inhibitory effect on the proliferation of human glioma ，and are better than suspension with higher dosage.
ABSTRACT
Objective The derivative of Gefitinib was used to treat glioma cells in vitro to explore a more effective new drug for the clinical treatment of astrocytoma. Methods (1) Fifteen kinds of gefitinib derivatives, gefitinib and temozolomide were used to treat glioma cells, and the effect of 0, 10, 15, 20, 25 and 30 μmol/L of each kind of drug on cell proliferation was detected by by MTT assay , respectively. (2) To calculate the concentration of IC50 , then select lower IC50 of derivativs combinate gefitinib and temozolomide with 10, 20 and 30 μmol/L to treat cells, then the apoptosis of cells were detected by flow cytometry. Expression of p-EGFR was detected by western–blot assay. Results (1) NO.LPY-5,9,11, but not other derivatives of Gefitinib could effectively inhibit the growth of cells. (2) IC50 of NO.LPY-9 was less than that of the 5th drug, and both of them were lower than those of gefitinib and temozolomide; NO. LPY-11 was excluded. (3) The cell apoptosis of No. LPY-9 was higher than that of gefitinib and temozolomide , respectively. However, No.LPY-9-induced cell apoptosis was significantly higher than that of No. LPY-5-induced cell. (4) Levels of p-EGFR expression in No.LPY-9 and gefitini-induced cells were significantly lower than that in the negative control group. Conclusion No.LPY-9 has asignificant inhibitory effect on glioma cells in vitro , resulting from the inhibition of the ERFR-mediated signaling pathways and induction of cell apoptosis.
ABSTRACT
To investigate the inhibitory effects of Ginsenoside Rb1 (GRb1) on apoptosis caused by Herpes Simplex Virus-1 (HSV-1) in Human Glioma Cells (U251),U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRb1,GRb1+HSV-1,HSV-1 and control groups.MTT and cell apoptosis assays were used to detect the inhibitory effects of GRbl on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay.We found that in the 400 μg/mL GRbl and 400 μg/mL GRbl+HSV-1 groups,MTT values were higher than control group at all times (P＜0.05).Moreover,the apoptosis rate in the 400 μg/mL GRb1+HSV-1 group was lower than the HSV-1 group (P＜0.05).These results confirmed that,at appropriate concentrations,GRb 1 could inhibit nerve cell apoptosis in HSV-1 infections.
ABSTRACT
Cyclooxygenase-1 (COX-1) and -2 (COX-2) are two isoforms of enzymes responsible for the biosynthesis of several forms of prostaglandins (PGs) from arachidonic acid. COX-1 is constitutively expressed in most normal tissues while COX-2 expression is regulated by certain stimuli such as cytokines and growth factors. The expression of COX-2 has been associated with many pathological conditions such as atherosclerosis, inflammation, and cancers (e.g. colon, breast, and lung cancers). COX-2 expression may be associated with the progression of cancers since PGE2, a major product of both isoforms was identified as a tumor-derived immune suppressor. Therefore, the suppression of COX-2 activity using specific COX-2 inhibitors (recently classified non-steroidal anti-inflammatory drugs) may delay the progression of tumors harboring COX-2. The search for tumors that highly express both isoforms of COX serves as a guide to target tumors that are most likely to be susceptible to treatment with specific COX-2 inhibitors. To study a homogeneous population of tumor cells, fifteen samples of primary culture cells were prepared from different human brain tissues and tumors collected from subjects operated on at Siriraj Hospital. Cells were grown to confluent in 75-cm2 tissue culture flask for about 4 weeks. After which time, cells were extracted to evaluate COX-1 and COX-2 protein expressions by immunoblot using specific antibodies. Four out of seven samples of glioblastoma multiforme cells strongly expressed COX-2, while all samples of examined cultured cells expressed COX-1. Cultured cells from astrocytomas had only faint staining for COX-2, while maintaining strong COX-1 expression. Thus COX-2 expression was limited to samples of glioblastoma multiforme, the most advanced stage of astrocytoma. Further study for the suppression of COX-2 activity in inducing tumor apoptosis and in improving cellular immunity against this advanced cancer should be elucidated.