Reference - Detail
| RRC ID | 76740 |
|---|---|
| Author | Tsuji K, Kikuchi E, Takashima Y, Shoji T, Takahashi H, Ito S, Morinaga D, Kashima M, Maeda M, Kitai H, Kikuchi J, Sakakibara-Konishi J, Konno S. |
| Title | Inhibition of non-homologous end joining mitigates paclitaxel resistance resulting from mitotic slippage in non-small cell lung cancer. |
| Journal | Cell Cycle |
| Abstract |
Mitotic slippage, which enables cancer cells to bypass cell death by transitioning from mitosis to the G1 phase without undergoing normal cytokinesis, is one likely mechanism of paclitaxel (PTX) resistance. DNA double-strand breaks (DSBs) in the G1 phase are mainly repaired through non-homologous end joining (NHEJ). Therefore, inhibiting NHEJ could augment the PTX-induced cytotoxicity by impeding the repair of PTX-induced DSBs during the G1 phase following mitotic slippage. We aimed to evaluate the effects of NHEJ inhibition on mitotic slippage after PTX treatment in non-small cell lung cancer (NSCLC). H1299, A549, H1975, and H520 NSCLC cell lines were employed. In addition, A-196 and JQ1 were used as NHEJ inhibitors. H1299 cells were PTX-resistant and exhibited an increased frequency of mitotic slippage upon PTX treatment. NHEJ inhibitors significantly augmented the PTX-induced cytotoxicity, DSBs, and apoptosis in H1299 cells. The newly generated PTX-resistant cells were even more prone to mitotic slippage following PTX treatment and susceptible to the combined therapy. Docetaxel further demonstrated synergistic effects with the NHEJ inhibitor in PTX-resistant cells. NHEJ inhibition may overcome intrinsic or acquired PTX resistance resulting from mitotic slippage by synergistically increasing the cytotoxic effects of antimitotic drugs in NSCLC. |
| Volume | 22(17) |
| Pages | 1854-1864 |
| Published | 2023-9-1 |
| DOI | 10.1080/15384101.2023.2243761 |
| PMID | 37592765 |
| PMC | PMC10599168 |
| MeSH | Antineoplastic Agents* / pharmacology Antineoplastic Agents* / therapeutic use Carcinoma, Non-Small-Cell Lung* / drug therapy Humans Lung Neoplasms* / drug therapy Mitosis Paclitaxel / pharmacology Paclitaxel / therapeutic use |
| IF | 4.238 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |