Abstract:

Abstract:Objective To study the inhibitory effects of tetraiodothyroacetic acid(Tetrac) on proliferation  of doxorubicin(Dox)-resistant human gastric cancer cell line SGC-7901/R in vitro and in vivo　and their action mechanisms.Methods Drug-sensitive(SGC-7901) and -resistant(SGC-7901/R) cells were cultivated  with different  concentrations of Dox or Tetrac for  4 d.The cell viability  was tested by MTT assay.Western blotting was used to detect the  expressions of P-gp,GST and SOD in drug-sensitive and drug-resistant  SGC-7901 cells.Dox-resistant SGC-7901/R cells were treated  with Tetrac either alone or in combination with each of Dox,etoposide (Etop),cisplatin (Cisp) 4 d later;the  cell viability,aging and apoptosis were  determined by  MTT assay,senescence-associated beta galactosidase (SA-b-Gal) and Hoechst staining.Nude mice were injected with Dox-resistant SGC-7901/R cells (10⁶/100  μL) and divided into 4 groups (n=7):saline control group,Tetrac (30 mg/kg^-1) group,Dox (2 mg/kg)  group and Tetrac (30 mg/kg) +Dox (2 mg/kg)  group.The growth of tumor in various groups was measured.Results The necrosis of two cell lines was significantly increased  with  the increasing of Tetrac concentrations,and all of them were dead  at 100 mg/L.The expression of drug resistance molecule P-gp was detected in SGC-7901/R cell line.The survival rates of SGC-7901/R cells after treated with Tetrac combined with each of Dox,Etop,Cisp or not were significantly decreased(P<0.001);the aging and death of SGC-7901/R cells after treated with Dox and Tetrac were significantly increased compared with using drug alone (P<0.05).In vivo study showed that  the growth of SGC-7901/R cells could be inhibited with Dox and Tectrac.Conclusion Tetrac can promote the aging and apoptosis of SGC-790/R cells by reducing the expression of drug resistance molecule P-gp, Tetrac is an effective chemotherapeutic agent in Dox-resistant cells.

Key words: tetraiodothyroacetic acid；stomach neoplasms；drug resistance