Downregulation of CPE regulates cell proliferation and chemosensitivity in pancreatic cancer
Pancreatic cancer (PC) is one of the most common cancers worldwide and a leading cause of cancer-related death. Discovering novel targets is a key for its therapy. Carboxypeptidase E (CPE), a subtype of the pro-protein convertases, has been shown to be upregulated in many types of cancer, yet its function in PC remains elusive. The expressions of CPE in PC cell lines and cancer patients were investigated by Western blot and qRT-PCR. In PC cell line BX-pc-3, CPE was downregulated and its effect on cancer cell proliferation, migration, cisplatin chemosensitivity, and in vivo tumor growth was analyzed by Western blot, proliferation assay, invasion assay, and in vivo transplantation, respectively. The expression of nuclear factor-kappaB (NF-κB), a possible downstream target of CPE was examined by Western blot upon CPE regulation in PC cells, and the effects of inhibiting NF-κB on PC cell invasion and proliferation were examined. CPE was significantly upregulated in PC cell lines and tumor tissues. Proliferation and invasion assays indicated that downregulation of CPE inhibited cancer cell growth and migration and increased chemosensitivity to cisplatin. Inoculation of small interfering RNA (siRNA) transfected BX-pc-3 cells into null mice demonstrated that downregulation of CPE prevented tumor growth in vivo. NF-κB was directly regulated by CPE in pancreatic cancer, and siRNA-mediated inhibition of NF-κB exerted similar anti-tumor effect as downregulating CPE. Taken together, our results demonstrate that CPE plays an important role in pancreatic cancer. Inhibition of CPE may serve as a potential target for PC therapeutics.
KeywordsPancreatic cancer CPE NF-κB
- 6.Satoh K. The molecular mechanism in tumorigenesis and development of pancreatic cancer. Nihon Shokakibyo Gakkai zasshi Jpn J Gastroenterol. 2013;110:2042–50.Google Scholar
- 13.Yang L, Zhou Z, Du T, Tan S, Zhnag Y, Jin P. Detection of carboxypeptidase h specific t cells in peripheral blood of latent autoimmune diabetic patients with carboxypeptidase antibody positivity by ELISPOT assay. Zhong nan da xue xue bao Yi xue ban J Cent South Univ Med Sci. 2009;34:1011–6.Google Scholar
- 25.Biliran Jr H, Wang Y, Banerjee S, Xu H, Heng H, Thakur A, et al. Overexpression of cyclin D1 promotes tumor cell growth and confers resistance to cisplatin-mediated apoptosis in an elastase-myc transgene-expressing pancreatic tumor cell line. Clin Cancer Res Off J Am Assoc Cancer Res. 2005;11:6075–86.CrossRefGoogle Scholar