Establishment of newly treatment strategies for suppressing desmoplasitic reactions in pancreatic cancer

我们研究了抗纤维化药物吡非尼酮（PF）是否抑制结缔组织增生并对胰腺癌产生抗肿瘤作用。PF对PSC的增殖、侵袭和迁移有明显的抑制作用，且呈剂量依赖性。用PF处理的PSC的上清液减弱促进胰腺癌细胞增殖、侵袭和迁移的能力。胰腺癌细胞培养上清可增加PSC中PDGF-A、HGF、I型胶原、Fibronectin和periostin的表达，PF可显著抑制这些表达。体内实验中，PF仅在与PSC共移植时才能显著抑制肿瘤生长，并减少肿瘤中PSC的数量和I型胶原及periostin的沉积。吉西他滨和PF联合治疗比单独吉西他滨和单独PF组更有效地抑制体内肿瘤生长。这些结果表明，PF可能是有前途的药物靶向结缔组织增生的抑制PSC和生产的生长因子和基质成分相关的肿瘤间质相互作用。

We investigated whether the antifibrotic agent, pirfenidone(PF), suppress desmoplasia and exert anti-tumor effects for pancreatic cancer. PF inhibited proliferation, invasiveness and migration of PSCs in the dose-dependent manner. The supernatants of PSCs treated with PF attenuated capacity to promote proliferation, invasiveness and migration of pancreatic cancer cells. The supernatants of pancreatic cancer cells increased production of PDGF-A, HGF, collagen type I, Fibronectin, and periostin in PSCs, and the increase were significantly reduced by PF. In vivo, PF significantly suppressed the tumor growth only when pancreatic cancer cells were co-transplanted with PSCs and decreased numbers of PSCs and deposition of collagen type I and periostin in tumors. Combination treatment with gemcitabine and PF more effectively suppressed in vivo tumor growth than gemcitabine alone and PF alone groups. These results indicate that PF could be promising agents targeting desmoplasia by suppression of PSCs and production of growth factors and stromal components related to tumor-stromal interactions.