The development of pancreatic cancer therapy based on regulating pancreatic cancer desmoplasia by targeting pancreatic stellate cells to improve drug delivery

通过靶向胰腺星状细胞改善药物输送来调节胰腺癌结缔组织形成的胰腺癌治疗的发展

• 批准号: 23659652
• 负责人: NAGAI Eishi
• 金额: $ 2.25万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659652/
• 关键词: 膵癌; 膵星細胞; ピルフェニドン; desmoplasia; pancreatic cancer; pirfenidone; gemcitabine; periostin

We indentified that the antifibrotic agent pirfenidone could suppress desmoplasia and exert anti-tumor effects against pancreatic cancer. In vitro, pirfenidone inhibited the proliferation, invasiveness, and migration of pancreatic stellate cells and tumor-stromal interaction between pancreatic stellate cells and pancreatic cancer cells. Oral administration of pirfenidone to the mice, which implanted with pancreatic cancer cells and pancreatic stellate cells, significantly reduced tumor growth. Pirfenidone also decreased the proliferation of pancreatic stellate cells, and inhibited the deposition of collagen type I and periostin in tumors. Pirfenidone in combination with gemcitabine more effectively suppressed tumor growth compared with pirfenidone or gemcitabine alone. Our findings indicate that pirfenidone is a promising antitumor agent for pancreatic cancer, owing to its suppression of desmoplasia through regulating pancreatic cancer cells.

我们发现抗纤维化药物吡非尼酮可以抑制结缔组织增生，并对胰腺癌发挥抗肿瘤作用。在体外，吡非尼酮抑制胰腺星状细胞的增殖、侵袭和迁移以及胰腺星状细胞和胰腺癌细胞之间的肿瘤-基质相互作用。对植入胰腺癌细胞和胰腺星状细胞的小鼠口服吡非尼酮显著降低了肿瘤生长。吡非尼酮还降低胰腺星状细胞的增殖，并抑制肿瘤中I型胶原和骨膜蛋白的沉积。与吡非尼酮或吉西他滨单独给药相比，吡非尼酮与吉西他滨联合给药更有效地抑制肿瘤生长。我们的研究结果表明，吡非尼酮是一个很有前途的胰腺癌抗肿瘤药物，由于其抑制结缔组织增生，通过调节胰腺癌细胞。

项目成果

Senescence in intraductal papillary mucinous neoplasm of the pancreas.

胰腺导管内乳头状粘液性肿瘤的衰老。

• 发表时间: 2011
• 期刊: Human Pathology
• 影响因子: 3.3
• 作者: Anazawa T;Sato Y;Saito T;Tsuchiya T;Kenjo A;Kimura T;Haga J;Miyake M;Waguri S;Hazama A;Gotoh M.;Miyasaka Y et al
• 通讯作者: Miyasaka Y et al

ntifibrotic Agent, Pirfenidone, Inhibits Pancreatic Stellate Cells and Tumor-Stromal Interaction in Pancreatic Cancer

抗纤维化剂吡非尼酮抑制胰腺癌中的胰腺星状细胞和肿瘤间质相互作用

• 作者: Kohei Nakata;Kenoki Ohuchida;Kazuhiro Mizumoto;Tadashi Kayashima;Naoki Ikenaga;Hiroshi Sakai;Cui Lin;Hayato Fujita;Takao Outsuka;Shinichi Aishima;Eishi Nagai;Yoshinao Oda;and Masao Tanaka.;Shingo Kozono
• 通讯作者: Shingo Kozono

Pirfenidoneによる膵星細胞を標的とした新しい膵癌治療の可能性

使用吡非尼酮针对胰腺星状细胞进行新的胰腺癌治疗的可能性

• 发表时间: 2012
• 作者: 小薗真吾;大内田研宙;水元一博;大塚隆生;赤川進;Ana Ines Cases;江口大樹;藤原謙次;趙茗;崔林;池永直樹;田中雅夫
• 通讯作者: 田中雅夫

MicroRNA expression as a predictive marker for gemcitabine response after surgical resection of pancreatic cancer.

胰腺癌手术切除后，microRNA表达是吉西他滨反应的预测标记。

• DOI: 10.1245/s10434-011-1602-x
• 发表时间: 2011-08
• 期刊: Annals of surgical oncology
• 影响因子: 3.7
• 作者: Ohuchida K;Mizumoto K;Kayashima T;Fujita H;Moriyama T;Ohtsuka T;Ueda J;Nagai E;Hashizume M;Tanaka M
• 通讯作者: Tanaka M

Pirfenidone inhibits proliferation, invasiveness, the chemokine and stromal component production of pancreatic satellate cells

吡非尼酮抑制胰腺卫星细胞的增殖、侵袭、趋化因子和基质成分的产生

• 发表时间: 2011
• 作者: Natsugoe S;Uenosono Y;Arigami T;Yanagita S;Haraguchi N;Kita Y;Uchikado Y;Okumura H;Matsumoto M;Ishigami S.;Tsutsumi K et al.;Kozono S et al
• 通讯作者: Kozono S et al