2017年7月
Bcl-2/Bcl-x(L) inhibitor ABT-737 sensitizes pancreatic ductal adenocarcinoma to paclitaxel-induced cell death
ONCOLOGY LETTERS
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 14
- 号
- 1
- 開始ページ
- 903
- 終了ページ
- 908
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.3892/ol.2017.6211
- 出版者・発行元
- SPANDIDOS PUBL LTD
Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignant disease that is resistant to various chemotherapeutic agents and commonly relapses. Efficient elimination of metastasized PDA is critical for a positive post-surgical treatment outcome. The present study analyzed the effect of the B-cell lymphoma-2 (Bcl-2)/B-cell lymphoma extra-large (Bcl-x(L) inhibitor, ABT-737, on paclitaxel-induced PDA cell death. A total of 8 PDA cell lines were subjected to immunoblotting to compare the expression of Bcl-2/Bcl-x(L) and other factors associated with taxane resistance, including myeloid cell leukemia 1 and beta III-tubulin (TUBB3). The viability of PDA cells was analyzed following treatment with paclitaxel alone or a combination treatment with ABT-737 and paclitaxel. Treatment with the ABT-737/paclitaxel combination induced PDA cell death at a lower concentration of paclitaxel compared with paclitaxel alone. In addition, the viable cell population at the saturation point of paclitaxel was also decreased by co-treatment with ABT-737. ABT-737 lowered the half maximal inhibitory concentration (IC50) by > 2-fold in PDA cells with high Bcl-2/Bcl-x(L) expression, but not in PDA cells with low Bcl-2/Bcl-x(L) expression and high TUBB3 expression. Knockdown of Bcl-x(L) lowered the IC50 of paclitaxel, but knockdown of TUBB3 did not. ABT-737 sensitized PDA to paclitaxel-induced cell death, and Bcl-x(L) expression was a key determinant of its sensitivity. ABT-737 is potential candidate for combination chemotherapy of PDA with high Bcl-x(L) expression levels.
- リンク情報
- ID情報
-
- DOI : 10.3892/ol.2017.6211
- ISSN : 1792-1074
- eISSN : 1792-1082
- PubMed ID : 28693250
- Web of Science ID : WOS:000405645800055