目的观察缺氧对胰腺癌细胞E-cadherin表达的抑制以及侵袭性生物学行为的影响,探讨E-cadherin表达抑制的调控机制。方法分别在常氧和缺氧环境下培养胰腺癌细胞Panc-1,通过Western blot和Transwell技术对比观察E-cadherin表达的差异以及细胞侵袭能力的变化。体外转染表达HIF-α siRNA的真核表达载体pGenesil-1-HIF-1α以及对照载体,进一步检测沉默HIF-α之后,Panc-1细胞E-cadherin和细胞侵袭能力的变化。结果缺氧可以抑制Panc-1细胞E-cadherin的表达,并增强其在体外的侵袭能力。而通过RNAi技术沉默了HIF-α之后,则可以部分恢复缺氧微环境对Panc-1细胞E-cadherin表达的抑制,同时降低其在体外的侵袭能力。结论缺氧微环境中HIF-α的活化可抑制E-cadherin的表达并加强胰腺癌细胞侵袭能力。
Objective To investigate the influence of hypoxia on E-cadherin and invasive behaviors of pancreatic carcinoma ceils. Methods The pancreatic cancer cell line Panc-1 was cultured under hypoxia and nomoxia. The expression of E-cadherin was detected by Western blot, and the invasion ability was determined by Transwell assay. The plasmid pGenesil-1-HIF-1α expressing shRNA targeted at HIF-1α gene and the control plasmid were transfected to silence the HIF-1α, and the E-cadherin and the invasive ability were determined accordingly. Results Hypoxia could suppress the expression of E-eadherin and enhance the invasive ability of Pane-1 cells. After silencing the expression of HIF-1α under hypoxia, the expression of E-cadherin could be enhanced and the invasive ability was inhibited. Condusion Hypoxia can promote the invasive ability of pancreatic cancer cells by activating HIF-1α and suppressing E-cadherin. The therapy targeting HIF-1α may provide a new weapon for overcoming pancreatic cancer.