CAJ | 학술논문

目的观察在胰腺癌和结肠癌的体外实验中，依维莫司( RAD001)发挥血管新生抑制作用的同时对5-氟尿嘧啶( 5-FU)是否有增敏效果。方法在体外细胞培养人胰腺癌AsPC、人结肠癌细胞HT29，并经大剂量放射线诱导建立放射耐受株AsPCres和HT29res，检测其中血管内皮生长因子(VEGF)和胸腺嘧啶磷酸化酶(TP)的表达情况；然后分别给予单独5-FU化疗，5-FU和mTOR抑制剂RAD001的联合化疗方案，观察肿瘤细胞的增殖情况。结果通过多个周期的大剂量放射诱导(3Gy)，可建立人胰腺癌放射耐受株AsPCres和人结肠癌放射耐受株HT29res；AsPCres和HT29res的VEGF的表达高于亲株，分别为(1215±67) pg/ml和(689±25) pg/ml，分别与各自亲株相比，差异有统计学意义，P＜0.01；放射耐受株的TP表达较亲株也有所上调；5- FU和mTOR抑制剂RAD001的联合方案可协同抑制肿瘤细胞的增殖，在HT29亲株和放射耐受株中，联合方案组(RAD001+5-FU)的细胞存活率分别为58.4％和75.9％,而单独5-FU给药组的细胞存活率分别为73.9％和87.4％。结论 mTOR抑制剂和5-FU的联合化疗方案可抑制放射耐受株肿瘤细胞的生长。这可能是RAD001抑制了肿瘤内放射诱导的VEGF表达；放射诱导肿瘤细胞上调TP的表达，使5-FU增敏。
목적 관찰재이선암화결장암적체외실험중，의유막사( RAD001)발휘혈관신생억제작용적동시대5-불뇨밀정( 5-FU)시부유증민효과。방법 재체외세포배양인이선암AsPC、인결장암세포HT29，병경대제량방사선유도건립방사내수주AsPCres화HT29res，검측기중혈관내피생장인자(VEGF)화흉선밀정린산화매(TP)적표체정황；연후분별급여단독5-FU화료，5-FU화mTOR억제제RAD001적연합화료방안，관찰종류세포적증식정황。결과 통과다개주기적대제량방사유도(3Gy)，가건립인이선암방사내수주AsPCres화인결장암방사내수주HT29res；AsPCres화HT29res적VEGF적표체고우친주，분별위(1215±67) pg/ml화(689±25) pg/ml，분별여각자친주상비，차이유통계학의의，P＜0.01；방사내수주적TP표체교친주야유소상조；5- FU화mTOR억제제RAD001적연합방안가협동억제종류세포적증식，재HT29친주화방사내수주중，연합방안조(RAD001+5-FU)적세포존활솔분별위58.4％화75.9％,이단독5-FU급약조적세포존활솔분별위73.9％화87.4％。결론 mTOR억제제화5-FU적연합화료방안가억제방사내수주종류세포적생장。저가능시RAD001억제료종류내방사유도적VEGF표체；방사유도종류세포상조TP적표체，사5-FU증민。
ObjectiveTo explore the in vitro synergistic anti-tumor efficacy of mammalian target of rampamycin (mTOR) inhibitor (RADO01) and 5-fluorouracil (5-FU) for radio-resistant tumors. Methods Radio-resistant cells of human pancreatic cancer cell and human colon cancer cell were established. The expression profiles of VEGF ( vascular endothelial growth factor) and TP ( thymidine phosphorylase) were compared between parental and radio-resistant tumor cells. The tumor proliferation was analyzed after 5-FU alone or in combination with a mTOR inhibitor. ResultsMter several cycles of radiation induction (3 Gy ),the radio-resistant ceils of human pancreatic cancer(AsPCres) and colon cancer(HT29res) were established.There was a higher expression of VEGF in radio-resistant tumor cells than their parental cells. They were 1215 ±67 pg/ml in AsPCres and 689 ±25 pg/ml in HT29res respectively (P ＜0. 01 ). The up-regulation of TP was observed in both AsPC-res and HT29-res. The combined therapy of 5-FU plus a mTOR inhibitor might exert synergistic tumor inhibition. ConclusionRAD001 decreases the radiation-induced expression of VEGF in tumor. And the post-radiation up-regulation of TP promotes the efficacy of 5-FU. The combined therapy of RAD001 and 5-FU may inhibit synergistically the growth of radio-resistant tumors.