| Objective To investigate the growth and angiogenesis effects of xenograft tumor which human gastric lower-differentiation mucinous carcinoma MGC803 cells inoculated into back subcutaneous of nude mice by using PPARγ ligand rosiglitazone(ROS) and all trans retinoic acid(ATRA) and explore the mechanism of anti-angiogenesis of ROS preliminarily.Methods First, cultivated the MGC803 cells and collected it to inoculate into back subcutaneous of nude mice(before inoculation weighted the mice). We observated the growth of the xenograft tumor, and screened the neoplasia mice. Second, two weeks after inoculation thirty-six male mice were divided into nine groups: no carcinoma(A), normal saline(B), mitomycin(C), rosiglitazone 100mg/kg(D1), rosiglitazone 50mg/kg(D2), rosiglitazone 25mg/kg(D3), rosiglitazone 50mg/kg and ATRA llmg/kg(E1), rosiglitazone 25mg/kg and ATRA11mg/kg(E2), rosiglitazone 18mg/kg and ATRA11mg/kg(E3). There are four mice in each group. Using the medicine after the xenograft tumor had grown to 100mm~3 . Mitomycin injected into abdominal cavity in C; poured the normal saline into stomach in B; and others were all poured the medicine into stomach. Measured the tumor volumes and weighted the mice every five days, then draw the growth curve of xenograft tumor and evaluated ill effect of the medicine. Third, after used medicine for fourty days, sacrificed the mice. Then measured tumor volumes of mice under the dissection microscope and inhibition tumor rates were calculated. Observated morphology andangiogenesis of the xenograft tumor by HE stain; The protein expression level of VEGF, HIF-la,CD34 were detected by immunohistochemical and calculated the difference of MVD; The mRNA expression level of VEGF, HIF-la were detected by RT-PCR assay accordingly.Results: 1. The weight of nude mice: Before sacrificed, weighted the nude mice, B was lighter than other groups(p<0.05); And the weights were no different between A and other groups.2. After using medication the effect to xenograft tumors: the difference of tumors volume were significance between B and other groups, and it was same at C, D3, E3 to other using medication groups (p<0.05).3.Observe the angiogenesis of xenograft tumors through morphology: HE stain were used to observe cancer cells were most abundance and there were most of the number of vascellums in B, then were C,D3,E3, and the angiogenesis is less in other groups.4. The expression of VEGF, HIF-la, CD34 protein: Immunohistochemical had discovered that VEGF and HIF-la were most expression in B, next were C, D3, E3, and the least expression in Dl and El. The difference was significance (p<0.05).5. The expression of VEGF, HIF-la mRNA: RT-PCR detection disclosed that the expression of mRNA of VEGF and HIF-la were highest in B, next were C, D3, E3, and other groups were lowest expression.Conclusion:1. The ROS which minimum concentration is 25mg/kg/2d could inhibit the growth of xenograft tumor, to accompany the increasing concentration of ROS the tumor control rate were correspond increasing. It is in concentration-dependent.2. Drug combinated of ROS and ATRA which minimum concentration is 18mg and llmg/kg/2d could decrease the dosage of ROS and achieved the similar result to inhibit the growth of tumor, it is possible relate to sensitization of ATRA.3. ROS alone or combinated with ATRA could decrease the expression of VEGF and inhibit the angiogenesis of tumor. There was positive correlation between the effect and dosage of drug in specified concentration.
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