Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer

Kazuhiko Kasuya, Akihiko Tsuchida, Yuichi Nagakawa, Minako Suzuki, Yuta Abe, Takao Itoi, Hiromi Serizawa, Toshitaka Nagao, Motohide Shimazu, Tatsuya Aoki

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

The normal pancreas has an abundant blood flow, in contrast to pancreatic cancer, which is a hypovascular tumor. During hypoxia under a hypovascular environment, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is activated. High HIF-1α expression reduces sensitivity to gemcitabine (GEM) which is used as a treatment for pancreatic cancer. The objective of this study was to clarify HIF-1α expression in pancreatic cancer and the association of its effects to GEM treatment. We used the human pancreatic ductal carcinoma cell lines AsPC-1 and BxPC-3 to evaluate cell proliferation, HIF-1α protein expression and sensitivity to GEM in a hypoxic environment of 1% O 2 in 48 pancreatic cancer patients who received adjuvant GEM treatment after pancreatectomy. We divided the patients according to HIF-1α expression and the presence of single nucleotide polymorphisms, and we based our evaluation on the adverse events associated with GEM chemotherapy and patient outcome. The hypoxic environment promoted cell proliferation, induced HIF-1α expression and increased GEM resistance, especially in AsPC-1 cells, which included a mutant homozygote for HIF-1α(C1772T). There were no significant differences between the HIF-1α(-) and HIF-1α(+) groups in either adverse events or patient outcomes. HIF-1α enhanced neo-microvascularity in a hypoxic environment and increased drug resistance. The period until recurrence was shorter in the patients with a strong HIF-1α expression, than that in those with a weak HIF-1α expression.

Original languageEnglish
Pages (from-to)1399-1406
Number of pages8
JournalOncology reports
Volume26
Issue number6
DOIs
Publication statusPublished - 2011 Dec

Keywords

  • Gemcitabine
  • HIF-1α
  • Pancreatic cancer
  • SNP

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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