Zuo J, Zhang C, Ren C, Pang D, Li Y, Xie X, Tang Z, Jiang X
Department of Stomatology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Clin Transl Oncol. 2015 Apr;17(4):314-21. doi: 10.1007/s12094-014-1232-4. Epub 2014 Oct 16.
A variety of inflammatory cytokines have been demonstrated to participate in tumorigenesis and progression. Secretory leukocyte protease inhibitor (SLPI) has been demonstrated to show a broad-spectrum of anti-inflammatory effects. This study investigates the expression of SLPI in human pancreatic cancer tissues and cells as well as its biological effects in human pancreatic cancer cells.
Reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot were used to detect SLPI mRNA and protein levels in human pancreatic cancer tissues, adjacent tissues, and pancreatic cancer Bxpc-3 and Panc-1 cells. Knockout of SLPI expression was established by recombinant viral vector expressing short hairpin RNA (shRNA) targeting SLPI. Cell viability was analyzed by MTT assay. Cell apoptosis was detected by Hochest33258 staining and flow cytometry assay.
Higher SLPI expression was observed in pancreatic tissues, Bxpc-3 cells, and Panc-1 cells compared to the peritumoral tissues (p < 0.01). SLPI expression in Bxpc-3 and Panc-1 cells was effectively silenced by shRNA (p < 0.001). Silencing of SLPI expression significantly reduced cell viability, inhibited cell proliferation, and induced cell apoptosis (p < 0.001).
Abnormal over-expression of SLPI in pancreatic cancer cells may be associated with the development of disease through its roles in promoting cancer cell survival and proliferation as well as anti-apoptosis. SLPI can be used as a target for developing targeted therapy of pancreatic cancer.
多种炎症细胞因子已被证明参与肿瘤的发生和发展。分泌型白细胞蛋白酶抑制剂(SLPI)已被证明具有广泛的抗炎作用。本研究旨在探讨SLPI在人胰腺癌组织和细胞中的表达及其对人胰腺癌细胞的生物学影响。
采用逆转录-聚合酶链反应、免疫组织化学和蛋白质印迹法检测人胰腺癌组织、癌旁组织以及胰腺癌细胞Bxpc-3和Panc-1中SLPI的mRNA和蛋白水平。通过表达靶向SLPI的短发夹RNA(shRNA)的重组病毒载体敲除SLPI的表达。采用MTT法分析细胞活力。通过Hochest33258染色和流式细胞术检测细胞凋亡。
与癌旁组织相比,在胰腺组织、Bxpc-3细胞和Panc-1细胞中观察到更高的SLPI表达(p<0.01)。shRNA有效沉默了Bxpc-3和Panc-1细胞中SLPI的表达(p<0.001)。SLPI表达的沉默显著降低了细胞活力,抑制了细胞增殖,并诱导了细胞凋亡(p<0.001)。
胰腺癌细胞中SLPI的异常过表达可能通过促进癌细胞存活、增殖以及抗凋亡作用参与疾病的发展。SLPI可作为开发胰腺癌靶向治疗的靶点。