Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in human esophageal carcinoma cell line
| Autor: | Weihua Liu, Tengjiao Yang, Kairui Zhou, Tiantian Qin, Jinling Huo, Sai-Qi Wang, Yinhui Dou, Xiaoli Shi, Liming Chang, Dongxiao Yang, Cong Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Small interfering RNA Esophageal Neoplasms Paclitaxel bcl-X Protein Apoptosis Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation In vivo Cell Line Tumor Carcinoma Humans Medicine ATP Binding Cassette Transporter Subfamily B Member 1 P-glycoprotein biology business.industry Bcl-2 family General Medicine medicine.disease Antineoplastic Agents Phytogenic Drug Resistance Multiple 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis biology.protein Myeloid Cell Leukemia Sequence 1 Protein business |
| Zdroj: | Biomedicine & Pharmacotherapy. 90:897-905 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2017.04.043 |
| Popis: | Paclitaxel (PTX) is one of the most effective drugs used in the treatment of esophageal cancer, however, paclitaxel resistance represents a key limitation during the treatment process. In this study, we investigated the changes of Bcl-2 family members in the moderate paclitaxel-resistance of esophageal carcinoma EC109/PTX cells both in vitro and in vivo. Moreover, we evaluated the reversal effect using siRNAs and the recombinant inhibitor TW37 targeting Bcl-2, Bcl-XL and Mcl-1. Our findings show that downregulation of Bcl-2, Bcl-XL and Mcl-1 can significantly promote EC109/PTX cell apoptosis and reduce the EC109/PTX cell resistance index (RI). Furthermore, TW37 in combination with a P-gp inhibitor can synergistically reverse the paclitaxel resistance in EC109/PTX cells. These results suggest that targeting of the Bcl-2 family and P-gp is capable of reversing the resistance in EC109/PTX cells and the two-inhibitor combination may be a novel treatment strategy for resistant esophageal cancer. |
| Databáze: | OpenAIRE |
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