Journal
TUMOR BIOLOGY
Volume 37, Issue 4, Pages 4323-4330Publisher
SPRINGER
DOI: 10.1007/s13277-015-4216-2
Keywords
SAHA; Erlotinib; E-cadherin; Human pancreatic cancer cells; Cell death
Categories
Funding
- Korea Health 21 R&D project, the Ministry of Health and Welfare and Family Affairs, Republic of Korea [HI06C0868]
- Basic Science Research Program through National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2013R1A1A2013233]
- Asan Institute for Life Sciences, Seoul, Republic of Korea [2014-231]
- National Research Foundation of Korea [2013R1A1A2013233] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Pancreatic cancer is one of the most lethal cancers and remains a major unsolved health problem. Less than 20 % of patients are surgical candidates, and the median survival for non-resected patients is approximately 3 to 4 months. Despite the existence of many conventional cancer therapies, few targeted therapies have been developed for pancreatic cancer. Combination therapy using erlotinib and gemcitabine is an approved standard chemotherapy for advanced pancreatic cancer, but it has marginal therapeutic benefit. To try to improve the therapeutic outlook, we studied the efficacy of another combination treatment and the relevance to E-cadherin in human pancreatic cancer cells. We treated two human pancreatic cancer cell lines with the histone deacetylase inhibitor (HDACi) SAHA. Interestingly, in these Panc-1 and Capan1 cells, we observed that the expression levels of E-cadherin and phosphorylated EGFR were gradually upregulated after treatment with SAHA. Furthermore, these cells underwent induced cell death after exposure to the combination treatment of SAHA and erlotinib. In Panc-1 cells, overexpression of E-cadherin activated the phosphorylation of EGFR and increased the cell sensitivity to erlotinib. In Capan1 cells, knocking down E-cadherin decreased the expression of phosphorylated EGFR, and these cells did not respond to erlotinib. Therefore, we demonstrated the efficacy of the combined treatment with SAHA and erlotinib in human pancreatic cancer cells, and we determined that the increased efficacy was due, at least in part, to the effects of SAHA on the expression of E-cadherin. Our studies suggest that E-cadherin may be a potent biomarker for pancreatic cancer.
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