Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via <i>B7H6</i> Suppression: A Novel Therapeutic Strategy
Purpose: Although chemotherapy is one of the standard treatments for gastric cancer, the disease’s resistance mechanisms continue to limit the survival rates. <i>B7H6</i> (<i>NCR3LG1</i>), an immune checkpoint belonging to the B7 family, is significantly overexpressed in gast...
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MDPI AG
2024-11-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/14/12/1546 |
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| author | Elif Sibel Aslan Nermin Akcali Cuneyd Yavas Sajjad Eslamkhah Savas Gur Lutfiye Karcioglu Batur |
| author_facet | Elif Sibel Aslan Nermin Akcali Cuneyd Yavas Sajjad Eslamkhah Savas Gur Lutfiye Karcioglu Batur |
| author_sort | Elif Sibel Aslan |
| collection | DOAJ |
| description | Purpose: Although chemotherapy is one of the standard treatments for gastric cancer, the disease’s resistance mechanisms continue to limit the survival rates. <i>B7H6</i> (<i>NCR3LG1</i>), an immune checkpoint belonging to the B7 family, is significantly overexpressed in gastric cancer. This work investigated the possibility of using <i>B7H6</i> suppression to improve the effectiveness of the widely used chemotherapy medication docetaxel. Materials and Methods: In this study, MKN-45 gastric cancer cells were transfected for 24 h with siRNA targeting <i>B7H6</i>, and then, docetaxel was added at optimal inhibitory doses (IC25 and IC50). To assess the impact of this combination therapy, cellular viability, proliferation, and migration were assessed using MTT assay, colony-forming unit assay, and wound-healing assay, respectively. Additionally, apoptosis and cell cycle status were evaluated by flow cytometry. Moreover, using qRT-PCR, the gene expression of <i>B7H6</i> and indicators associated with apoptosis was also examined. Results: The sensitivity of MKN-45 cells to docetaxel was greatly increased by the siRNA-mediated knockdown of <i>B7H6</i>, resulting in a decrease in the drug’s IC50 value. When compared to each therapy alone, the combination of <i>B7H6</i> siRNA plus docetaxel at IC50 levels exhibited a significant increase in apoptosis rate. The volume of cells arrested at the sub-G1 and G2-M phase was shown to rise when <i>B7H6</i> siRNA transfection was combined with docetaxel. Furthermore, the combination treatment significantly decreased the ability of cells to migrate and form colonies. Conclusions: <i>B7H6</i> suppression increases the susceptibility of MKN-45 gastric cancer cells to docetaxel treatment, resulting in decreased cellular proliferation and increased rates of apoptosis. The present work underscores the possibility of enhancing treatment results in gastric cancer by merging conventional chemotherapy with gene-silencing approaches. |
| format | Article |
| id | doaj-art-e7ae93492a204edd898a349d58ac865e |
| institution | OA Journals |
| issn | 2075-1729 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj-art-e7ae93492a204edd898a349d58ac865e2025-08-20T02:00:23ZengMDPI AGLife2075-17292024-11-011412154610.3390/life14121546Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via <i>B7H6</i> Suppression: A Novel Therapeutic StrategyElif Sibel Aslan0Nermin Akcali1Cuneyd Yavas2Sajjad Eslamkhah3Savas Gur4Lutfiye Karcioglu Batur5Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Biruni University, Istanbul 34015, TürkiyeFaculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Biruni University, Istanbul 34015, TürkiyeFaculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Biruni University, Istanbul 34015, TürkiyeFaculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Biruni University, Istanbul 34015, TürkiyeInternal Medicine Specialist, Private Clinic, Çanakkale 17100, TürkiyeFaculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Biruni University, Istanbul 34015, TürkiyePurpose: Although chemotherapy is one of the standard treatments for gastric cancer, the disease’s resistance mechanisms continue to limit the survival rates. <i>B7H6</i> (<i>NCR3LG1</i>), an immune checkpoint belonging to the B7 family, is significantly overexpressed in gastric cancer. This work investigated the possibility of using <i>B7H6</i> suppression to improve the effectiveness of the widely used chemotherapy medication docetaxel. Materials and Methods: In this study, MKN-45 gastric cancer cells were transfected for 24 h with siRNA targeting <i>B7H6</i>, and then, docetaxel was added at optimal inhibitory doses (IC25 and IC50). To assess the impact of this combination therapy, cellular viability, proliferation, and migration were assessed using MTT assay, colony-forming unit assay, and wound-healing assay, respectively. Additionally, apoptosis and cell cycle status were evaluated by flow cytometry. Moreover, using qRT-PCR, the gene expression of <i>B7H6</i> and indicators associated with apoptosis was also examined. Results: The sensitivity of MKN-45 cells to docetaxel was greatly increased by the siRNA-mediated knockdown of <i>B7H6</i>, resulting in a decrease in the drug’s IC50 value. When compared to each therapy alone, the combination of <i>B7H6</i> siRNA plus docetaxel at IC50 levels exhibited a significant increase in apoptosis rate. The volume of cells arrested at the sub-G1 and G2-M phase was shown to rise when <i>B7H6</i> siRNA transfection was combined with docetaxel. Furthermore, the combination treatment significantly decreased the ability of cells to migrate and form colonies. Conclusions: <i>B7H6</i> suppression increases the susceptibility of MKN-45 gastric cancer cells to docetaxel treatment, resulting in decreased cellular proliferation and increased rates of apoptosis. The present work underscores the possibility of enhancing treatment results in gastric cancer by merging conventional chemotherapy with gene-silencing approaches.https://www.mdpi.com/2075-1729/14/12/1546gastric cancerdocetaxel<i>B7H6</i> suppressionchemosensitivitysiRNA-mRNA |
| spellingShingle | Elif Sibel Aslan Nermin Akcali Cuneyd Yavas Sajjad Eslamkhah Savas Gur Lutfiye Karcioglu Batur Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via <i>B7H6</i> Suppression: A Novel Therapeutic Strategy Life gastric cancer docetaxel <i>B7H6</i> suppression chemosensitivity siRNA-mRNA |
| title | Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via <i>B7H6</i> Suppression: A Novel Therapeutic Strategy |
| title_full | Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via <i>B7H6</i> Suppression: A Novel Therapeutic Strategy |
| title_fullStr | Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via <i>B7H6</i> Suppression: A Novel Therapeutic Strategy |
| title_full_unstemmed | Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via <i>B7H6</i> Suppression: A Novel Therapeutic Strategy |
| title_short | Enhancing the Chemosensitivity of MKN-45 Gastric Cancer Cells to Docetaxel via <i>B7H6</i> Suppression: A Novel Therapeutic Strategy |
| title_sort | enhancing the chemosensitivity of mkn 45 gastric cancer cells to docetaxel via i b7h6 i suppression a novel therapeutic strategy |
| topic | gastric cancer docetaxel <i>B7H6</i> suppression chemosensitivity siRNA-mRNA |
| url | https://www.mdpi.com/2075-1729/14/12/1546 |
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