Small molecule inhibitor TW-37 is tolerable and synergistic with chemotherapy in nasopharyngeal carcinoma
| Autor: | Jiang Zhou, Ying Lu, Haixin Huang, Dagui Chen, Hui Yang, Wu Sibei, Rensheng Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Databases Factual medicine.medical_treatment Apoptosis Mice 0302 clinical medicine Sulfones Mice Inbred BALB C Nasopharyngeal Carcinoma Cell Cycle Drug Synergism Gene Expression Regulation Neoplastic Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Benzamides Drug Therapy Combination Fluorouracil medicine.drug Signal Transduction Cell Survival Mice Nude Antineoplastic Agents Biology 03 medical and health sciences In vivo Report Cell Line Tumor Adjuvant therapy medicine otorhinolaryngologic diseases Animals Humans Viability assay Molecular Biology Cell Proliferation Cisplatin Chemotherapy Carcinoma Cancer Nasopharyngeal Neoplasms Cell Biology medicine.disease Xenograft Model Antitumor Assays stomatognathic diseases 030104 developmental biology Nasopharyngeal carcinoma Cancer research Myeloid Cell Leukemia Sequence 1 Protein Developmental Biology |
| Popis: | Chemotherapy is a crucial adjuvant therapy of advanced nasopharyngeal carcinoma (NPC). However, enhancing sensitivity and tolerance of chemotherapeutics in NPC treatment have been challenging. Both Bcl-2 and Mcl-1, 2 pro-survival proteins of Bcl-2 family, play essential roles on the chemotherapy tolerance of numerous cancers. In the present study, we explored the influences of TW-37, a small molecule inhibitor of Bcl-2 and Mcl-1, on the efficiency of chemotherapy for NPC. Oncomine cancer database shows that NPC tissues have higher expression of Bcl-2 and Mcl-1 than those of normal nasopharyngeal epithelial (NPE) tissues. And our results reveal that chemotherapeutics, Cisplatin (CDDP) and 5-Fluoracil (5-FU), result in the greater decrease of protein level of Bcl-2 and Mcl-1 in NPC cells than those in NPE cells. TW-37 does not have significant impact on the chemotherapeutics-treated NPE cell viability at a dosage that efficiently reduces chemotherapeutics-treated NPC cell viability. Moreover, impacts of TW-37 on the cell viability of chemotherapeutics-treated NPC cells are dependent on the expression of Bcl-2 and Mcl-1 in NPC cells. Further explorations suggest that TW-37 prominently promotes apoptosis in NPC cells under chemotherapeutics treatments but not in NPE cells. Meanwhile, TW-37 also remarkably reduces colony formation ability of chemotherapeutics-treated NPC cells. Importantly, in vivo models, TW-37 observably increases chemosensitivity of NPC tumors but has not markedly influence on the normal tissues in mice. In conclusion, our results point to TW-37 as a promising ancillary drug for the chemotherapy of NPC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|