The Effects Of Human Digestive System Tumor Cells Differentiation Induced By 4-Amino-2-Trifluoromethyl-Phenyl Retinate And Its Influence On Retinoid Acid Receptors And Retinoid X Receptors

Objective: To investigate the proliferation inhibition and differentiation induction activities of 4-amino-2-trifluoromethyl-phenyl retinate(ATPR) in human gastric cancer cells SGC-7901, human liver cancer cells Bel-7402, HEPG2,human colon carcinoma cells HT-29,ovarian cancer SKOV3.Explore the mechanisms of ATPR partly.Methods:1..Cell proliferation was assessed by MTT assay before and after the treatment with ATPR in vitro. Morphologic changes were observed after Giemsa staining using inverted phase contrast microscope.ALP,LDH andγ-GT were measured by spectrophotometer for enzyme activity; AFP, CEA and CA125 were measured by ELISA; The cell cycle was analyzed by flow cytometry.2. The expression of RARα,RARβ,RARγ,RXRαmRNA treatment without ATPR were detected by RT-PCR and compare the differences.3. The expression of RARα,RARβ,RARγ,RXRαmRNA after the treatment with ATPR for 72h were detected by RT-PCR . Results:1.The growth of SGC-7901,Bel-7402,HEPG2, HT-29,SKOV3 cells were inhibited in a does-dependent manner after the treatment with ATPR.The phanero depressant effect appeared at 48 hours ,but it is significanter after 72 hours.Cell morphous was observed to be mature in inverted microscope. ALP and LDH activity of SGC-7901 suppressant;AFP,LDH andγ-GT of Bel-7402 and HEPG2 decreased; SKOV3 with the content of CA125 decreased while the expression of CEA of HT-29 increased.G₀/G₁-phase cells were significantly increased while S-phase cells were decreased with the elevation of ATPR concentration. Cell cycle progression was blocked in the G₁ phase.2. The expression of RARβof five tumor cells were little or even deletion.The expression of RARαwas high in BEL-7402 cell and HEPG2 cell. The expression of RARγwas highest in SGC-7901 cell. RXRαin SGC-7901, BEL-7402, HEPG2, SKOV3 cells have a higher expression, but the expression in HT-29 were relatively low.3. The expression of RARαand RARβwere increased while the expression of RARγand RXRαwere decreased in SGC-7901 cells after treat with ATPR for 72h. The expression of RARαwas decreased while the expression of RARβand RARγwere increased in BEL-7402 and HEPG2 cells. The expression of RARs were increased in HT-29 cells. The expression of RARαwas increased while RXRαwas d ecreased in SKOV3 cells.Conclusion:1. ATPR could inhibit the proliferation and induce differentiation tumor cells in some degree.But the differentiation of HT-29 is still need further study.2. Retinoid acid receptors and retinoid X receptors distributed variously in solid tumor cells and had quite different levels. The difference of distribution reflected the difference of accepted retinoic acid regulation ability by these cells. The different ratio among different subtypes in retinoic acid receptor may be is an important reason for tumor cells induced different sensitivity differentiation by retinoic acid and ATPR.3. Receptors RARα, RARβ, RARγand RXRαmay had closely relation of growth inhibition and differentiation treat with ATPR on SGC-7901 gastric cancer cell line. Receptors RARα, RARβand RARγmay had closely relation of growth inhibition and differentiation on BEL-7402 and HEPG2 cells. Receptors RARα, RARβand RARγmay had closely relation of growth inhibition and differentiation on HT-29 cells.Receptors RARαand RXRαmay had closely relation of growth inhibition and differentiation on SKOV3 cells. But their exact relationships still need to be further confirmed.