| Author |
Park, Seong Joon Kim, Seung-Mi Moon, Jai-Hee Kim, Jeong Hee Shin, Jae-Sik Hong, Seung-Woo Shin, Yu Jin Lee, Dae-Hee Lee, Eun Young Hwang, Ih-Yeon Kim, Jeong Eun Kim, Kyu-Pyo Hong, Yong Sang Lee, Won-Keun Choi, Eun Kyung Lee, Jung Shin Jin, Dong-Hoon Kim, Tae Won |
| Description |
Author Affiliation: Park SJ ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.); Kim SM ( Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.); Moon JH ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.); Kim JH ( Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.); Shin JS ( Department of Biosciences and Bioinformatics, Myongji University, 116 Myongji-ro, Cheoin-gu, Yongin-si, Gyeonggi-do, 449-728, Republic of Korea.); Hong SW ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.); Shin YJ ( Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.); Lee DH ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.); Lee EY ( Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.); Hwang IY ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.); Kim JE ( Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.); Kim KP ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.); Hong YS ( Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.); Lee WK ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.); Choi EK ( Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.); Lee JS ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.); Jin DH ( Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.); Kim TW ( Innovative Cancer Research, ASAN Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.) |
| Abstract |
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. |
