Paclitaxel pretreatment overcomes hypoxia inducible factor-1α-induced radioresistance acquisition of human hepatoma and lung adenocarcinoma cells

Kun Goung Lai, Yi Hsien Lin, Chun Te Ho, Chun Yi Chen, Chu Ying Peng, Tsan Zon Liu, Jeng Fong Chiou

研究成果: 雜誌貢獻文章同行評審

8 引文 斯高帕斯(Scopus)

摘要

Aims This study delineated the mechanisms of paclitaxel (PTX) assistance in overcoming radioresistance in hepatoma and human lung adenocarcinoma (HLAC) cells. Main methods The TUNEL assay was used as an index of radiosensitivity, and the MTT assay assessed the efficacy of various combined PTX/RT treatments. The efficacy of PTX disruptions of hypoxia-inducible factor-1 alpha (HIF-1α) was assessed using Western blotting. Key findings Normoxically overexpressed HIF-1α in hepatoma J5 cells was mechanistically linked to activation of the bFGF/PI3K/Akt pathway because the viability of these cells was strongly inhibited by either Akt inhibitors or an HIF-1α inhibitor. All of the cell lines used were extremely sensitive to PTX, and these effects also correlated excellently with HIF-1α suppression. We designed five combined radiation-PTX protocols of varying dose duration and treatment sequences against CL1-1 cells based on the gathered data. Pretreatment of CL1-1 cells with PTX (100 nM) for 24 h before irradiation (2.5 Gy) was the best combined protocol to achieve maximum radiosensitizing effects. Significance Our data clearly indicate that PTX pretreatment is an effective radiosensitizing procedure against HIF-1α-expressing hepatoma and HLAC cells, which are constitutively endowed with radioresistance.

原文英語
頁(從 - 到)7-12
頁數6
期刊Life Sciences
136
DOIs
出版狀態已發佈 - 七月 11 2015

ASJC Scopus subject areas

  • 藥理學、毒理學和藥劑學 (全部)
  • 生物化學、遺傳與分子生物學 (全部)
  • 醫藥 (全部)

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