Reference - Detail
| RRC ID | 68432 |
|---|---|
| Author | Suzuki S, Yamamoto M, Sanomachi T, Togashi K, Seino S, Sugai A, Yoshioka T, Okada M, Kitanaka C. |
| Title | Lurasidone Sensitizes Cancer Cells to Osimertinib by Inducing Autophagy and Reduction of Survivin. |
| Journal | Anticancer Res |
| Abstract |
BACKGROUND/AIM:Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are key drugs in cancer treatment due to their minor adverse effects and outstanding anticancer effects. However, drugs for overcoming EGFR-TKI resistance are not in clinical use so far. Therefore, to overcome resistance, we focused on lurasidone, a new antipsychotic drug, due to its mild adverse effect profile from the viewpoint of drug repositioning. MATERIALS AND METHODS:We explored the effects of lurasidone alone or in combination with EGFR-TKI on the growth of osimertinib-resistant cancer cells the anti-apoptotic marker expression such as survivin, and autophagy levels by LC-3B expression. RESULTS:Within a non-toxic concentration range in normal cells, lurasidone and osimertinib combination therapy showed a growth-inhibitory effect in osimertinib-resistant cancer cells in vitro and in vivo. Furthermore, lurasidone decreased survivin expression and mildly induced autophagy. CONCLUSION:Lurasidone may increase the sensitivity to osimertinib in osimertinib-resistant cancer cells in drug repurposing. |
| Volume | 41(9) |
| Pages | 4321-4331 |
| Published | 2021-9-1 |
| DOI | 10.21873/anticanres.15237 |
| PII | 41/9/4321 |
| PMID | 34475052 |
| MeSH | A549 Cells Acrylamides / administration & dosage* Acrylamides / pharmacology Aniline Compounds / administration & dosage* Aniline Compounds / pharmacology Animals Autophagy / drug effects Carcinoma, Non-Small-Cell Lung / drug therapy* Carcinoma, Non-Small-Cell Lung / metabolism Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Down-Regulation Drug Resistance, Neoplasm / drug effects* Drug Synergism Gene Expression Regulation, Neoplastic / drug effects Humans Lung Neoplasms / drug therapy* Lung Neoplasms / metabolism Lurasidone Hydrochloride / administration & dosage* Lurasidone Hydrochloride / pharmacology Mice Microtubule-Associated Proteins / metabolism Survivin / metabolism* Xenograft Model Antitumor Assays |
| IF | 1.994 |
| Resource | |
| Human and Animal Cells | A549(RCB0098) |