The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines

被引：2

作者：

Denda, Yuki ^{[1
]}

Matsuo, Yoichi ^{[1
]}

Sugita, Saburo ^{[1
]}

Eguchi, Yuki ^{[1
]}

Nonoyama, Keisuke ^{[1
]}

Murase, Hiromichi ^{[1
]}

Kato, Tomokatsu ^{[1
]}

Imafuji, Hiroyuki ^{[1
]}

Saito, Kenta ^{[1
]}

Morimoto, Mamoru ^{[1
]}

Ogawa, Ryo ^{[1
]}

Takahashi, Hiroki ^{[1
]}

Mitsui, Akira ^{[1
]}

Kimura, Masahiro ^{[1
]}

Takiguchi, Shuji ^{[1
]}

机构：

[1] Nagoya City Univ, Grad Sch Med Sci, Dept Gastroenterol Surg, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, 4678601, Japan

来源：

NUTRIENTS | 2024年 / 16卷 / 05期

基金：

日本学术振兴会;

关键词：

parthenolide; pancreatic cancer; gemcitabine resistance; NF-kappa B; invasion; angiogenesis; ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; SESQUITERPENE LACTONE; MULTIDRUG-RESISTANCE; THERAPY; EXPRESSION; INTERLEUKIN-1-ALPHA; TRANSPORTERS; BURDEN; KINASE;

D O I：

10.3390/nu16050705

中图分类号：

R15 [营养卫生、食品卫生]; TS201 [基础科学];

学科分类号：

100403 ;

摘要：

We previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor kappa B (NF-kappa B) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor activity by suppressing the NF-kappa B signaling pathway in several types of cancers. However, the antitumor effect of parthenolide on gemcitabine-resistant PaCa has not been elucidated. Here, we confirmed that parthenolide significantly inhibits the proliferation of both gemcitabine-resistant and normal PaCa cells at concentrations of 10 mu M and higher, and that the NF-kappa B activity is significantly inhibited, even by 1 mu M parthenolide. In Matrigel invasion assays and angiogenesis assays, the invasive and angiogenic potentials were higher in gemcitabine-resistant than normal PaCa cells and were inhibited by a low concentration of parthenolide. Furthermore, Western blotting showed suppressed MRP1 expression in gemcitabine-resistant PaCa treated with a low parthenolide concentration. In a colony formation assay, the addition of 1 mu M parthenolide improved the sensitivity of gemcitabine-resistant PaCa cell lines to gemcitabine. These results suggest that parthenolide may be used as a novel therapeutic agent for the treatment of gemcitabine-resistant PaCa.

引用

页数：16

共 60 条

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