四碘甲腺乙酸对耐药性人胃癌细胞系体内和体外增殖的抑制作用

目的：研究四碘甲腺乙酸(Tetrac)对阿霉素(Dox)抵抗性人胃癌细胞系SGC-7901/R体内及体外扩增的抑制作用及作用机制。方法：体外实验分为SGC-7901与SGC-7901/R两组，分别与不同浓度的Tetrac和Dox共同培养4 d。MTT法检测其细胞活性，以不同药物浓度下的肿瘤细胞存活率来表示；Western blotting检测2组中相关耐药基因P-gp、SOD和GST的表达。分别将Dox、依拉泊苷(Etop)、顺铂(Cisp)3种药物单独或联合Tetrac作用于SGC-7901/R细胞系，用MTT法、衰老相关的β-半乳糖苷酶(SA-b-Gal）染色法与凋亡相关的烟酸已可碱（Hoechst）染色法检测肿瘤细胞活性、衰老及凋亡情况，检测结果以染色阳性细胞比例表示。体内实验中，腋部皮下注射SGC-7901/R细胞（10⁶ /100 μL）的裸鼠被分成4组（每组7只）：生理盐水对照组、Tetrac治疗组（30 mg/kg）、Dox治疗组（2 mg/kg）和Tetrac（30 mg/kg）+Dox（2 mg/kg）联合药物治疗组，检测各组小鼠肿瘤生长情况。结果：体外实验中，2组肿瘤细胞均随Tetrac浓度的升高而坏死明显加快，在100 mg/L时全部死亡；P-gp转运子仅在SGC-7901/R细胞中过表达；Dox、Etop、Cisp与 Tetrac联合用药时，SGC-7901/R细胞存活率较单独用药明显降低(P<0.001)；Dox与Tetrac联合用药时，SGC-7901/R细胞衰老、死亡较单独用药明显增加(P<0.05)。体内实验中，Dox与Tetrac联合用药可以明显抑制肿瘤生长。结论：Tetrac可能通过降低药物转运子P-gp表达来促进SGC-7901/R细胞的衰老和凋亡，对于治疗Dox抵抗性肿瘤是一种有效的化疗药物。

Inhibitory effect of tetraiodothyroacetic acid on proliferation of drug- resistant human gastric cancer cell line in vivo and in vitro

Objective To study the inhibitory effects of tetraiodothyroacetic acid(Tetrac) on proliferation of doxorubicin(Dox)-resistant human gastric cancer cell line SGC7901/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-1) and divided into 4 groups(n=7):saline control group,Tetrac(30 mg·kg-1) group,Dox(2 mg·kg-1) group and Tetrac(30 mg·kg-1) +Dox (2 mg·kg-1) 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-1.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.