[RAD001 reverses radio-resistance and exerts synergistic tumor inhibition with 5-fluorouracil].

ABSTRACT

OBJECTIVE: To explore the in vitro synergistic anti-tumor efficacy of mammalian target of rampamycin (mTOR) inhibitor (RAD001) 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. RESULTS: After several cycles of radiation induction (3 Gy), the radio-resistant cells 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. CONCLUSION: RAD001 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.