Cheng Hao, Zhu Hao, Cao Meng, Lu Chenglin, Bao Shanhua, Pan Yiming
Department of General Surgery, The Afflicted Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Department of Gastroenterology, The Afflicted Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Braz J Med Biol Res. 2018 Nov 23;52(1):e7718. doi: 10.1590/1414-431X20187718.
Pancreatic cancer is well known to be the most deadly malignancy with the worst survival rate of all cancers. High temperature requirement factor A1 (HtrA1) plays an important role in cancer cell proliferation, migration, apoptosis, and differentiation. This study aimed to explore the function of HtrA1 in pancreatic cancer cell growth and its underlying mechanism. We found that the expression of HtrA1 was lower in pancreatic cancer tissue compared to the adjacent normal tissue. Consistently, HtrA1 levels were also decreased in two human pancreatic cancer cell lines, PANC-1 and BXPC-3. Moreover, enforced expression of HtrA1 inhibited cell viability and colony formation of PANC-1 and BXPC-3 cells. Overexpression of HtrA1 promoted apoptosis and suppressed migratory ability of tumor cells. On the contrary, siRNA-mediated knockdown of HtrA1 promoted the growth potential of pancreatic cancer cells. In addition, we found that up-regulation of HtrA1 reduced the expression of Notch-1 in pancreatic cancer cells. On the contrary, knockdown of HtrA1 increased the expression levels of Notch-1. Furthermore, overexpression of Notch-1 abolished the anti-proliferative effect of HtrA1 on pancreatic cancer cells. Taken together, our findings demonstrated that HtrA1 could inhibit pancreatic cancer cell growth via regulating Notch-1 expression, which implied that HtrA1 might be developed as a novel molecular target for pancreatic cancer therapy.
众所周知，胰腺癌是最致命的恶性肿瘤，在所有癌症中生存率最差。高温需求因子A1（HtrA1）在癌细胞的增殖、迁移、凋亡和分化中起重要作用。本研究旨在探讨HtrA1在胰腺癌细胞生长中的作用及其潜在机制。我们发现，与相邻正常组织相比，胰腺癌组织中HtrA1的表达较低。同样，在两种人胰腺癌细胞系PANC-1和BXPC-3中，HtrA1水平也降低。此外，HtrA1的强制表达抑制了PANC-1和BXPC-3细胞的活力和集落形成。HtrA1的过表达促进了肿瘤细胞的凋亡并抑制了其迁移能力。相反，siRNA介导的HtrA1敲低促进了胰腺癌细胞的生长潜力。此外，我们发现HtrA1的上调降低了胰腺癌细胞中Notch-1的表达。相反，HtrA1的敲低增加了Notch-1的表达水平。此外，Notch-1的过表达消除了HtrA1对胰腺癌细胞的抗增殖作用。综上所述，我们的研究结果表明，HtrA1可通过调节Notch-1表达来抑制胰腺癌细胞生长，这意味着HtrA1可能成为胰腺癌治疗的新型分子靶点。
