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SN-38 Acts as a Radiosensitizer for Colorectal Cancer by Inhibiting the Radiation-induced Up-regulation of HIF-1α.

Abstract：

BACKGROUND/AIM:Hypoxia offers resistance to therapy in human solid tumors. The aim of the study was to investigate whether SN-38, the active metabolite of irinotecan, acts as a radiosensitizer through inhibition of hypoxia-inducible factor (HIF)-1α in the human colorectal cancer (CRC) cells. MATERIALS AND METHODS:HT29 and SW480 cells were cultured with SN-38 (0-4 μM) immediately after irradiation (0-8 Gy). HIF-1α expression was assessed using flow-cytometry and western blot analysis. Cell proliferation was evaluated by the calcein assay. Apoptosis and cell cycle were determined by flow-cytometry. RESULTS:Radiation up-regulated HIF-1α, and SN-38 inhibited the radiation-induced HIF-1α. The combination of radiation and SN-38 inhibited cell proliferation more than radiation alone; treatment with SN-38 after radiation exposure did not increase the number of apoptotic cells, whereas, it enhanced the S and G2/M cell-cycle arrest and decreased the population of cells in G1 Conclusion: SN-38 inhibits the radiation-induced up-regulation of HIF-1α and acts as a radiosensitizer by inducing cell-cycle arrest in CRC cells.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Okuno T,Kawai K,Hata K,Murono K,Emoto S,Kaneko M,Sasaki K,Nishikawa T,Tanaka T,Nozawa H

doi

10.21873/anticanres.12598

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

3323-3331

issue

6

eissn

0250-7005

issn

1791-7530

pii

38/6/3323

journal_volume

38

pub_type

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