RRC ID 52624
著者 Mao Y, Huang X, Shuang Z, Lin G, Wang J, Duan F, Chen J, Li S.
タイトル PARP inhibitor olaparib sensitizes cholangiocarcinoma cells to radiation.
ジャーナル Cancer Med
Abstract Cholangiocarcinoma (CCA) is a highly malignant tumor with resistance to radiotherapy alone. Olaparib, a highly potent poly(ADP-ribose) polymerase (PARP) inhibitor, has been shown to sensitize many types of tumor to radiotherapy. However, the effect of olaparib, either as monotherapy or as combination therapy with radiotherapy, on CCA is not known, and our study aimed to explore this. To assess radiosensitization in three CCA cell lines (QBC939, HuH28 and TFK-1), viability and clonogenic assays were conducted. The absorbed radiation doses were 0 Gy, 2 Gy, 4 Gy, and 6 Gy; olaparib concentrations were 0 nmol/L, 1 nmol/L, 10 nmol/L, 100 nmol/L, 1000 nmol/L, 2500 nmol/L, 5000 nmol/L and 10 000 nmol/L. The mechanism of olaparib radiosensitization was explored by Western blotting. Immunofluorescence staining and flow cytometry were conducted to explore DNA damage and apoptosis. The radiosensitivity of CCA cells was enhanced by olaparib, which alone had little effect on the CCA cell lines without BRCA mutations. The degree of radiosensitization increased with increasing doses of olaparib by viability and clonogenic assays in vitro. Olaparib was able to enhance the effect of radiation by inhibiting PARP1, inducing DNA lesions and apoptosis. These findings emphasize the role of olaparib in the radiosensitization of CCA cells.
巻・号 7(4)
ページ 1285-1296
公開日 2018-4-1
DOI 10.1002/cam4.1318
PMID 29479816
PMC PMC5911590
MeSH Antineoplastic Agents / pharmacology* Apoptosis Biomarkers, Tumor Cell Line, Tumor Cell Survival / drug effects Cholangiocarcinoma Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Genes, BRCA1 Genes, BRCA2 Histones / metabolism Humans Loss of Function Mutation Phthalazines / pharmacology* Piperazines / pharmacology* Poly(ADP-ribose) Polymerase Inhibitors / pharmacology* Radiation Tolerance / drug effects Radiation-Sensitizing Agents / pharmacology*
IF 3.491
引用数 8
リソース情報
ヒト・動物細胞 HuH-28(RCB1943)