Je Dong Wook, O Young Moon, Ji Young Geon, Cho Yunkyung, Lee Dong Hyeon
From the Departments of *Physiology, †Preventive Medicine, and ‡Internal Medicine, School of Medicine, CHA University, Seongnam, Gyeonggi, South Korea.
Pancreas. 2014 Jul;43(5):768-76. doi: 10.1097/MPA.0000000000000103.
Src is considered a rising therapeutic target for the treatment of solid tumors, and Src family kinases (SFKs) participate in cancer cell proliferation and survival. The role of SFK suppression was investigated in the proliferation, migration, and invasion of pancreatic cancer cells.
Knockdown of the SFKs in pancreatic cancer cells was achieved by transfecting small interfering RNAs, and its effects were investigated using proliferation, wound, and invasion assays.
The SFK inhibitors suppressed proliferation and induced cell cycle arrest in pancreatic cancer cells. The SFK messenger RNA profiles showed that Yes1, Lyn, Fyn, Frk, Hck, and Src were expressed. Specific small interfering RNA transfection suppressed the messenger RNA expressions of Yes1, Lyn, Fyn, Frk, and Src, and the knockdown suppressed cell proliferation by 16.7% to 47.3% in PANC-1 cells. Knockdown of any of these 5 SFKs suppressed proliferation in other pancreatic cancer cell lines by 3.0% to 40.5%. The knockdowns significantly reduced pancreatic cancer cell migration by 24.9% to 66.7% and completely inhibited invasion.
These results suggest that the knockdown of Yes1, Lyn, Fyn, Frk, or Src reduce human pancreatic cancer cell proliferation, migration, and invasion, and that SFKs should be viewed as critical therapeutic targets of pancreatic cancer.
Src被认为是实体瘤治疗中一个新兴的治疗靶点，Src家族激酶（SFKs）参与癌细胞的增殖和存活。本研究探讨了抑制SFK对胰腺癌细胞增殖、迁移和侵袭的作用。
通过转染小干扰RNA实现胰腺癌细胞中SFKs的敲低，并利用增殖、创伤和侵袭实验研究其作用效果。
SFK抑制剂抑制胰腺癌细胞的增殖并诱导细胞周期停滞。SFK信使RNA谱显示Yes1、Lyn、Fyn、Frk、Hck和Src有表达。特异性小干扰RNA转染抑制了Yes1、Lyn、Fyn、Frk和Src的信使RNA表达，在PANC-1细胞中，这种敲低使细胞增殖抑制了16.7%至47.3%。敲低这5种SFKs中的任何一种均可使其他胰腺癌细胞系的增殖抑制3.0%至40.5%。敲低显著降低胰腺癌细胞迁移24.9%至66.7%，并完全抑制侵袭。
这些结果表明，敲低Yes1、Lyn、Fyn、Frk或Src可降低人胰腺癌细胞的增殖、迁移和侵袭，并且SFKs应被视为胰腺癌的关键治疗靶点。
