Effects Of Two Platinum Compounds On The Expression Of Livin And MDR1 In Gastric Cancer Cells

Background and objective: The incidence of gastric cancer is high inChina. The ultimate defeat of AGC (advanced gastric cancer) was usuallychemotherapy resistance. MDR1 gene and apoptosis defect accounts forsome of chemotherapy resistance. IAP (inhibitor of apoptosis protein)family, which plays an important role in the apoptosis defect, has been thefocus of research recently. Livin was one of novel IAP members. Therelationship between Livin and the prognosis of the therapy for gastriccancer remains unclear. Meanwhile the relationship between MDR1 andL-OHP (Oxaliplatin) requires an in-depth study. CDDP (Cisplatin) andL-OHP with different mechanisms of action are all efficacious for gastriccancer. The aim of this study was to investigate: (1) The growth inhibitionof gastric cancer cells (BGC-823 and SGC-7901) after the treatment byL-OHP and CDDP. (2) The expression of Livin and MDR1 gene inducedby the two platinum compounds in human gastric cancer cells (BGC-823and SGC-7901). (3) The different mechanism of action for the gastric cancer cells with the two platinum compounds.Methods: (1) The proliferation inhibition ratio of gastric cancer cells(BGC-823 and SGC-7901) was evaluated by MTT after the treatment byone of the two platinum compounds for different time respectively. (2)Different inhibiting concentration (IC10, IC30 or IC50) of the twoplatinum compounds was added into the medium of BGC-823 andSGC-7901 cells. The expression of Livin and MDR1 gene was detectedby RT-PCR. (3) Inhibiting concentrations 30 (IC30) of the two platinumcompounds was added into the medium of BGC-823 and SGC-7901 cellsfor 24, 48 and 72 hours. The protein level of Livin was assessed byWestern Blots. (4) Inhibiting concentrations 30 (IC30) of the twoplatinum compounds was added into the medium of BGC-823 andSGC-7901 cells for 48 hours. FCM was enrolled to detect apoptosis in thetwo cells. (5) Inhibiting concentrations 30 (IC30) of the two platinumcompounds was added into the medium of BGC-823 and SGC-7901 cellsfor 48 hours. Cell Scratch Test evaluated cell migration ability.Results: (1) The proliferation of BGC-823 and SGC-7901 was inhibitedin a dose- and time-dependent manner after the treatment of CDDP orL-OHP, especially the latter was dose-dependent more significantly thanthe former. (2) In BGC-823 (a poorly differentiated cell line), theexpression of Livin, which was down-regulated by the two platinumcompounds in the earlier period, was up-regulated after 72 hours by CDDP, not by L-OHP. In SGC-7901 (a moderately differentiated cellline), the expression of Livin, which was lower than that in BGC-823,was up regulated with CDDP and in the earlier period with L-OHP. ButLivin was down regulated significantly after 72 hours with L-OHP inSGC-7901. (3) After the treatment by two platinum compounds, MDR1were all up regulated in the two cells. (4) After the treatment by twoplatinum compounds, the apoptosis level of BGC-823 was significanctlyhigher than that of SGC-7901. Meanwhile, the apoptosis level by L-OHPwas significanctly higher than by CDDP. (5) After the treatment by twoplatinum compounds, BGC-823 group had the slower and shorterdistance immigration than SGC-7901 group. Meanwhile, it had the fasterand longer distance immigration by CDDP than by L-OHP.Conclusions: (1) Increased dosage of L-OHP was more powerful incytotoxicity than that of CDDP possibly within a range, as for theinhibition of proliferation in vitro. L-OHP induced apoptosis andsuppressed cell migration more significantly than CDDP. (2) L-OHP is apotent inhibitor of Livin in gastric cancer cells possibly. Livin can delaythe drug resistance possibly. CDDP can induce the expression of Livin ingastric cancer cells, which may participate in the drug resistance insomeway. (3) The two platinum compounds inhibited proliferation andinduced apoptosis. It was more efficiently in the poorly differentiated cellthan in the moderately one. The latter acquired resistance easilier than the former. The expression of Livin in moderately differentiated cells waslower than in poorly differentiated cells. Livin in the former can be upregulated more significantly than the latter after the treatment by CDDP.The degree of cell differentiation could be correlated with Livin. (4) Thetwo platinum compounds could induce the expression of MDR1. Theresistance mechanism of platinum compounds might be related withMDR1.