| Objective: To investigate reversing drug-resistant and its mechanisms in human gastric cancer SGC7901/VCR cells induced by diallyl disulfide.Methods:Using MTT measurement, the dose-response curve of DADS in SGC7901 and SGC7901/VCR cells was drawn, the sensitivity of 5-FU on SGC7901/VCR cells were determined as well as resistant factor. MDR-reversing effect of DADS on the SGC7901/VCR cells. The influence of DADS on SGC7901 and SGC7901/VCR cell apoptosis was determined by flow cytometry. The influence of DADS on SGC7901/VCR cell apoptosis was determined by AO-EB fluorescent staining. With the RT-PCR method, the mRNA level of MDR-1 gene was determined. With the western-blot method, the p-gp protein expression was determined.Results:1. Diallyl disulfide showed noobvious toxieity to SGC7901/VCR and SGC7901cell under the dose of 8mg·L-1, and its toxicity showed dose effete once over this concentration;the IC50 of DADS to SGC7901/VCR cell line and SGC7901 cell line are 49.55 mg·L-1 and 45.21 mg·L-1 respectively, the two groups had no statistical significance (P>0.05). The IC50 of 5-FU to SGC7901/VCR cell line and SGC7901 cell line are 209.78 mg·L-1 and 34.16 mg·L-1 respectively, the multiple of drug resistance is 6. 14, the two groups had statistical significance (P<0.01). Under the action of 8mg·L-1DADS, the sensitivity of the drug-resistant cell SGC7901/VCR enhanced to 5-FU, the IC50 decreased signifieantly (P<0.001), was 73.57 mg·L-1. 5-FU and DADS drug combination are possess synergistic action.2. Flow cytometry results that: after 48h the treatment of 8mg·L-1 DADS on SGC7901/VCR cells, the apoptotic rate of SGC7901/VCR group, 5-FU group, DADS group, 5-FU+ DADS group were respectively (1.75士0.61)%,(4.95士0.14)%,(14.60士0.30)%,(22.60土0.20)%. DADS group, DADS+5-Fu group can increase the apoptotic rate of SGC7901/VCR cell line, compared with blank controland and 5-Fu groups, the difference had obvious statistical significance (P<0.01).3. AO-EB fiuorescent staining results that: after 48h the treatment of 8mg·L-1 DADS on SGC7901/VCR cells, the apoptotic rate of SGC7901/VCR group, 5-FU group, DADS group, 5-FU+ DADS group were respectively 3.9%,8.25%,23.50%,31.50%。DADS group, DADS+5-Fu group can increase the apoptotic rate of SGC7901/VCR cell line, compared with blank controland and 5-Fu groups, the difference had obvious statistical significance (P<0.01).4.RT-PCR results that: after 48h the treatment of 8mg·L-1 DADS on SGC7901/VCR cells, the mdr1/β-actin ratio of SGC7901 group, SGC7901/VCR group, 5-FU group, DADS group, 5-FU+ DADS group were respectively 0.457±0.673,0.881±0.543,0.860±0.380,0.635±0.140,0.585±0.214.The expression of MDR-1 mRNA gene of SGC7901/VCR cell line in DADS and DADS+5-Fu groups is down-regulate than blank controland and 5-Fu groups, the difference had statistical signifieance (P<0.05).5.Western-blot results that: after 48h the treatment of 8mg·L-1 DADS on SGC7901/VCR cells, the P-gp/β-actin ratio of SGC7901/VCR group, SGC7901 group, 5-FU group, DADS group, 5-FU+ DADS group were respectively 0.457±0.673,0.881±0.543,0.860±0.380,0.635±0.140,0.585±0.214.The expression of P-gp protein of SGC7901/VCR cell line in DADS and DADS+5-Fu groups is down-regulate than blank controland and 5-Fu groups, the difference had statistical signifieance (P<0.05).Conelusions:1. DADS inhibits the growth of SGC7901 cells and SGC7901/VCR cells at 8mg·L-1, 16mg·L-1, 32mg·L-1 and 64mg·L-1, And has no drug resistance in SGC7901/VCR cells. 2. DADS can reserve the drug resistance of SGC7901/VCR cells to 5-Fu partly. 5-FU and DADS drug combination are possess synergistic action.3. DADS can induce the apoptosis and Gi-phase arresting in SGC7901/VCR cells4. The over expression of multidrug resistance gene MDR1and p-gp protein is apossible reason of multidrug resistance of SGC79OI/VCR cells.5. DADS can down- regulate the expression of MDR1 gene and p-gp protein, this maybe an important mechanism of DADS reversing multidrug resistance of SGC7901/VCR cells partly.
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