STE029 Overcomes EGFR-TKI Resistance in Human Lung Adenocarcinoma
| Title: | STE029 Overcomes EGFR-TKI Resistance in Human Lung Adenocarcinoma |
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| Authors: | Lin HUANG, Mei HOU, Jiewei LIU, Yang LI, Wang SHEN, Qinghua ZHOU |
| Source: | Chinese Journal of Lung Cancer, Vol 25, Iss 11, Pp 771-781 (2022) |
| Publisher Information: | Chinese Anti-Cancer Association; Chinese Antituberculosis Association, 2022. |
| Publication Year: | 2022 |
| Collection: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | ste029, egfr-tki, resistance, apoptosis, cell cycle, lung adenocarcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | Background and objective Acquired and primary resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is still the bottleneck of clinical treatment of advanced non-small cell lung cancer (NSCLC). STE029 is a novel anticancer drug which consists of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) inhibitor and novel cancer cell membrane targeting molecular. This study aimed to investigate the reversal mechanism of EGFR-TKI resistance by STE029 in lung adenocarcinoma. Methods CCK8 test was used to test the cell viability and survival rate of EGFR mutated PC9 cell (Gefitinib sensitive), PC9/BB4 cell (acquired Gefitinib resistant), and EGFR wild type A549 cell after treatment of STE029, Gefitinib or combination of both. EdU test was applied to detect changes in cell cycle and Hoechst 33258 was applied to detect apoptosis rate in overcoming the EGFR-TKI resistance. The activity of EGFR/PI3K/Akt, cell cycle and apoptosis signal pathways were examined. In vivo, nude mice were exposed to STE029, Gefitinib and STE029+Gefitinib for 5 wk. And the the tumor volume was measured and tumor weight was obtained on the last day. Results (1) PC9 cells was highly sensitive to Gefitinib, while PC9/BB4 and A549 cell showed significant resistance to Gefitinib treatment; (2) STE029+Gefitinib treatment could significantly decrease the 50% inhibitory concentrarion (IC50) of Gefitinib in PC9, PC9/BB4 and A549 cells (P0.05); However, apoptosis rate was increased in STE029+Gefitinib group in A549 cell (P0.05). (4) In PC9 and PC9/BB4 cells, the combination of STE029 and Gefitinib could downregulate p-EGFR, p-Akt, p-Cyclin D1 and Cyclin D1 (P0.05). In A549 cells, the combination of STE029 and Gefitinib could downregulate p-Akt (P |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | Chinese |
| ISSN: | 1009-3419 1999-6187 |
| Relation: | https://doaj.org/toc/1009-3419; https://doaj.org/toc/1999-6187 |
| DOI: | 10.3779/j.issn.1009-3419.2022.102.46 |
| Access URL: | https://doaj.org/article/c4cd868706bc48c391c4ecdcbc7d8040 |
| Accession Number: | edsdoj.4cd868706bc48c391c4ecdcbc7d8040 |
| Database: | Directory of Open Access Journals |
| ISSN: | 10093419 19996187 |
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| DOI: | 10.3779/j.issn.1009-3419.2022.102.46 |
| Published in: | Chinese Journal of Lung Cancer |
| Language: | Chinese |