RRC ID 52352
著者 Endo S, Nakata K, Sagara A, Koikawa K, Ando Y, Kibe S, Takesue S, Nakayama H, Abe T, Okumura T, Moriyama T, Miyasaka Y, Ohuchida K, Ohtsuka T, Mizumoto K, Nakamura M.
タイトル Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells.
ジャーナル Pancreatology
Abstract BACKGROUND:Salinomycin has cytotoxic effects on various types of malignancy and induces autophagy. However, it has not been clarified whether autophagy induced by salinomycin treatment has a protective or cytotoxic role. We investigated whether salinomycin affects autophagy in pancreatic cancer cells and whether autophagy induced by salinomycin treatment has a protective or cytotoxic role in these cells.
METHODS:We investigated the effect of salinomycin using three pancreatic cancer cell lines. We investigated effect on proliferation and the CD133 positive fraction using flow cytometry. In addition, we monitored the change in autophagic activity after salinomycin treatment using fluorescent immunostaining, western blotting, and flow cytometry. Finally, knockdown of ATG5 or ATG7 by siRNA was used to investigate the impact of autophagy inhibition on sensitivity to salinomycin.
RESULTS:Salinomycin suppressed the proliferation of pancreatic cancer cells in a concentration dependent manner, and reduced the CD133 positive fraction. Salinomycin enhanced autophagy activity in these cells in a concentration dependent manner. Autophagy inhibition made pancreatic cancer cells more sensitive to salinomycin.
CONCLUSIONS:Our data provide the first evidence indicating that autophagy induced by salinomycin have a protective role in pancreatic cancer cells. A new therapeutic strategy of combining salinomycin, autophagy inhibitors, and anticancer drugs could hold promise for pancreatic cancer treatment.
巻・号 17(6)
ページ 990-996
公開日 2017-1-1
DOI 10.1016/j.pan.2017.08.009
PII S1424-3903(17)30743-3
PMID 28927939
MeSH Autophagy / drug effects* Cell Line, Tumor Cell Proliferation / drug effects* Cell Survival / drug effects Dose-Response Relationship, Drug Humans Pancreatic Neoplasms / drug therapy* Pyrans / administration & dosage Pyrans / pharmacology*
IF 3.241
引用数 8
リソース情報
ヒト・動物細胞 PANC-1(RCB2095)