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 language | English |
|---|---|
| Pages (from-to) | 1399-1406 |
| Number of pages | 8 |
| Journal | Oncology Reports |
| Volume | 26 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2011 Dec |
| Externally published | Yes |
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Keywords
- Gemcitabine
- HIF-1α
- Pancreatic cancer
- SNP
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer. / Kasuya, Kazuhiko; Tsuchida, Akihiko; Nagakawa, Yuichi; Suzuki, Minako; Abe, Yuta; Itoi, Takao; Serizawa, Hiromi; Nagao, Toshitaka; Shimazu, Motohide; Aoki, Tatsuya.
In: Oncology Reports, Vol. 26, No. 6, 12.2011, p. 1399-1406.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hypoxia-inducible factor-1α expression and gemcitabine chemotherapy for pancreatic cancer
AU - Kasuya, Kazuhiko
AU - Tsuchida, Akihiko
AU - Nagakawa, Yuichi
AU - Suzuki, Minako
AU - Abe, Yuta
AU - Itoi, Takao
AU - Serizawa, Hiromi
AU - Nagao, Toshitaka
AU - Shimazu, Motohide
AU - Aoki, Tatsuya
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Gemcitabine
KW - HIF-1α
KW - Pancreatic cancer
KW - SNP
UR - http://www.scopus.com/inward/record.url?scp=80053532392&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053532392&partnerID=8YFLogxK
U2 - 10.3892/or.2011.1457
DO - 10.3892/or.2011.1457
M3 - Article
VL - 26
SP - 1399
EP - 1406
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 6
ER -