RAD001 shows activity against gastric cancer cells and overcomes 5-FU resistance by downregulating thymidylate synthase |
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| Authors: | Kyung-Hun Lee Hyung-Seok Hur Seock-Ah Im Juhee Lee Hwang-Phill Kim Young-Kwang Yoon Sae-Won Han Sang-Hyun Song Do-Youn Oh Tae-You Kim Yung-Jue Bang |
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| Affiliation: | 1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea;2. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea;3. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Republic of Korea |
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| Abstract: | We evaluated RAD001, an inhibitor of the mammalian target of rapamycin (mTOR) in human gastric cancer cell lines and determined the molecular mechanisms. RAD001 has marked growth inhibitory activity against the SNU-1 and SNU-216 cells. It inhibited phosphorylation of mTOR and S6 K, and induced G1 cell cycle arrest. Synergistic growth-inhibitory effects in combination with 5-fluorouracil (5-FU) was identified. Furthermore, RAD001 conferred sensitivity to 5-FU-resistant cell lines by downregulating thymidylate synthase (TS). In conclusion, RAD001 showed growth inhibitory activity against gastric cancer cells and acted synergistically with cytotoxic agents such as 5-FU by downregulating TS. |
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| Keywords: | Gastric cancer RAD001 mTOR Thymidylate synthase |
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