HSP90 inhibition downregulates thymidylate synthase and sensitizes colorectal cancer cell lines to the effect of 5FU-based chemotherapy
作者： Ganji Purnachandra Nagaraju , Olatunji B. Alese , Jerome Landry , Roberto Diaz , Bassel F. El-Rayes
关键词:
摘要: Cell cycle progression and DNA synthesis are essential steps in cancer cell growth. Thymidylate synthase (TS) is a therapeutic target for 5FU. We tested the hypothesis that HSP90 transcriptional functional inhibition can inhibit progression, downregulate TS levels sensitize colorectal (CRC) lines to effects of Treatment with ganetespib (50nM) 24 hours inhibited cyclin D1 pRb at translational induced p21, leading G0/G1 arrest both CRC (HCT-116 HT-29). This was associated downregulation E2F1 its gene TS. In addition, PI3K/Akt ERK signalling pathways. Similar were observed knockdown lines. Ganetespib sensitized oxaliplatin also tumors from animals treated ganetespib, this study, we present vitro animal data supporting targeting decreases survival proliferation. sensitizes 5FUbased chemotherapy. Combining inhibitors chemotherapy rational approach future drug development CRC.
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