Anti-tumor Effects of Erlotinib via Thymidylate Synthase Down-regulation in Pancreatic Cancer Cells.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2025-02-01 DOI:10.21873/anticanres.17439

Satoshi Tabuchi, Tetsuro Tominaga, Tomoshi Tsuchiya, Ryoichiro Doi, Jyunichi Arai, Takashi Nonaka, Takuro Miyazaki, Tatsuo Inamine, Kazuhiro Tsukamoto, Keitaro Matsumoto

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引用次数: 0

Abstract

Background/aim: In pancreatic cancer, gemcitabine and EGFR tyrosine kinase inhibitors (EGFR-TKIs) are common chemotherapy options. Reports have shown that EGFR-TKIs suppress the expression of thymidine synthase (TS), an important enzyme for DNA biosynthesis, and increase sensitivity to gemcitabine in lung cancer. However, no such reports have been made in pancreatic cancer.

Materials and methods: Human pancreatic cancer cell lines MiaPaCa2, Panc1, and BxPc3 were used. TS mRNA and protein expression levels in the cells were analyzed after erlotinib treatment. In addition, the anti-tumor effect of TS knockdown was verified using TS siRNA, along with its synergistic effect when combined with gemcitabine.

Results: TS expression was high in MiaPaCa2 and Panc1 cells and low in BxPc3 cells. After erlotinib treatment, TS mRNA and protein levels decreased markedly in MiaPaCa2 cells dose-dependently, but not in Panc1 cells. TS siRNA caused specific down-regulation of TS in MiaPaCa2 and Panc1 cells. TS down-regulation resulted in an anti-tumor effect in these cells (MiaPaCa2 42%; Panc1 38%; p<0.05), showing a synergistic effect when combined with gemcitabine.

Conclusion: Erlotinib could have a synergistic anti-tumor effect when combined with gemcitabine via down-regulation of TS expression.

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.