Department of General Surgery, QiLu Hospital of Shandong University, Jinan 250012, P.R. China.
Anticancer Res. 2010 Jan;30(1):135-42.
Integrin alphavbeta6 is up-regulated in a variety of human carcinomas and plays a crucial role in tumor invasion and metastasis. However, the function of alphavbeta6 in pancreatic carcinoma and its potential role in gemcitabine resistance remain unknown.
Small interfering RNA (siRNA) targeting alphavbeta6 was constructed and transfected into PANC-1 cells. Effects of alphavbeta6 knockdown on cell proliferation, invasion, cell cycle progression, apoptosis and chemosensitivity to gemcitabine were investigated.
Expression of alphavbeta6 in PANC-1 cells was markedly suppressed by siRNA. Silencing of alphavbeta6 expression significantly inhibited cell proliferation and invasiveness, resulted in cell cycle arrest, and induced cell apoptosis. More importantly, alphavbeta6 knockdown enhanced chemosensitivity to gemcitabine and increased gemcitabine-induced caspase-mediated apoptosis.
These findings suggest a novel mechanism by which alphavbeta6 contributes to pancreatic carcinoma progression. The combination of alphavbeta6 silencing and gemcitabine treatment may provide an effective therapeutic strategy for highly resistant pancreatic carcinoma.
整合素 alphavbeta6 在多种人类癌中上调，并在肿瘤侵袭和转移中发挥关键作用。然而，alphavbeta6 在胰腺癌中的功能及其在吉西他滨耐药中的潜在作用尚不清楚。
构建了针对 alphavbeta6 的小干扰 RNA（siRNA）并转染至 PANC-1 细胞。研究了 alphavbeta6 敲低对细胞增殖、侵袭、细胞周期进程、凋亡和吉西他滨化疗敏感性的影响。
siRNA 显著抑制了 PANC-1 细胞中 alphavbeta6 的表达。沉默 alphavbeta6 表达显著抑制细胞增殖和侵袭，导致细胞周期停滞，并诱导细胞凋亡。更重要的是，alphavbeta6 敲低增强了吉西他滨的化疗敏感性，并增加了吉西他滨诱导的 caspase 介导的细胞凋亡。
这些发现提示了 alphavbeta6 促进胰腺癌进展的新机制。alphavbeta6 沉默和吉西他滨治疗的联合可能为高度耐药的胰腺癌提供一种有效的治疗策略。
