The Correlative Mechanism Of Inducing Apoptosis In Astric Carcinoma Transplated Into Mice By Rosiglitazone

Objective To explore whether Rosiglitazone(ROS),a selective Peroxisome proliferator-activated receptor gamma (PPARγ) ligand, can reverse the resistance to Mitomycin (MMC) of human gastric cancer SGC7901/VCR cell line transplated into mice which has multidrug resistant phenotype, and further to explore the possible mechanism of ROS reserving multidrug resistance in apoptosis.Methods To establish mouse gastric model by subcutaneous injection of SGC7901/VCR cells suspension nude mice, and observation the growth of the xenograft tumor, then screening the neoplasia mice. Two weeks after surgery forty-eight male nude mice were divided into six groups: normal saline 0.2ml.2d^-1(A) ,mitomycin 2.5mg.kg^-1.2d^-1(B), rosiglitazo ne100mg.kg^-1. 2d^-1(C), ros iglitazone50mg.kg^-1.2d^-1+mitomycin2.5mg.kg^-1.2d^-1(D),rosiglitazone100mg.kg^-1.2d^-1+mitomycin2.5mg.kg^-1.2d^-1(E) , cyclosporine A(CSA)50mg.kg^-1.2d^-1+mito mycin2.5 mg.kg^-1.2d^-1(F). There are eight mice in each group, when the xenograft tumor growth to 100mm3 beginning to use medicine. Mitomycin injected into abdominal cavity , and others were all pour the normal saline or medicine into stomach. Measured the tumor volumes and weighted the mice every five days, then draw the growth curve of xenograft tumor. Third, after used medicine for forty days, sacrificed the mice and tumor volumes were measured and inhibition tumor rates were calculated. Observated apoptosis of the xenograft tumor by DNA ladder; The transcription of P-Akt,Bcl-2,Bax-Ag mRNA were meansured by Real Time-PCR .The expression of protein of P-Akt,Bcl-2,Bax -Ag were detected by western-blot.Results1. The weight of nude mice: the difference of the average Tralantabletumor weight in the blank group and other groups were not statistically different before executed(P>0.05); 2. After medication the effect on the volume of Tralantabletumor : there was no significant difference between group A and group B(P>0.05). the difference of tumors volume were significance between other groups compared with group A and group B (P<0.05), the least volume in group E and group F;3. DNA ladder demonstrated that:there was no obviously apoptosis in group A and B,while there was weak apoptosis in group C,combined MMC and ROS , apoptosis gradually enhanced, along with ROS raised, show obvious DNA Ladder,and group F equal to group E;4. The effect on the transcription of P-Akt,Bcl-2,BaxmRNA after medication: The expression mRNA of P-Akt,Bcl-2-Ag was highest in group A and group B; there was significant difference among group A and groupB(P>0.05),group C,D,E were gradually decreased, there was significant difference among them(P<0.05);The expression mRNA of P-Akt,Bcl-2-Ag was lowest in group E and group F,there was no significant difference among group E and F(P>0.05)。however, The expression mRNA of Bax were least in group A. there was no significant difference among group B and group A(P>0.05); group C, D and group E gradually enhanced, there was significant difference among them(P<0.05);The expression mRNA of Bax was highest in group E and group F,there was no significant difference among group E and F(P>0.05)。5.After medication the effect on the protein expression of P-Akt,Bcl-2,Bax-Ag: The protein expression of P-Akt,Bcl-2-Ag was highest in group A and group B there was significant difference among group A and groupB(P>0.05),group C,D,E were gradually decreased, there was significant difference among them(P<0.05);The protein expression of P-Akt,Bcl-2-Ag was lowest in group E and group F, there was no significant difference among group E and F(P>0.05);Bax protein expression in the group A were least,there was no significant difference among group B and A(P>0.05), group C, D, E gradually enhanced, there was significant difference among them(P<0.05)。The expression of Bax protein was highest in group E and group F,there was no significant difference among group E and F(P>0.05)。ConclusionRosiglitazone inhibits the growth of tralantabletumor of SGC7901/VCR; Rosiglitazone can induce apoptosis in human gastric cancer SGC7901/VCR cell line transplated into mice; Rosiglitazone can reserve the drug resistance of tralantabletumor of SGC7901/VCR cell line to MMC partly in vivo.Rosiglitazone can down-regulate the expression of p-Akt, Bcl-2-Ag gene and its encoding protein and up-regulate Bax gene and its encoding protein in the xenograft tumor, this maybe an important mechanism of ROS inducing apoptosis of SGC7901/VCR cell line partly in vivo.