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新型 4-噻唑烷酮衍生物与抗 HER2 抗体在人 AGS 胃癌细胞中的多靶点抗癌活性。

Multi-Targeting Anticancer Activity of a New 4-Thiazolidinone Derivative with Anti-HER2 Antibodies in Human AGS Gastric Cancer Cells.

机构信息

Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, 15-089 Bialystok, Poland.

Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland.

出版信息

Int J Mol Sci. 2023 Apr 5;24(7):6791. doi: 10.3390/ijms24076791.

DOI:10.3390/ijms24076791
PMID:37047765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10095353/
Abstract

Combining chemotherapy with immunotherapy still remains a regimen in anticancer therapy. Novel 4-thiazolidinone-bearing hybrid molecules possess well-documented anticancer activity, and together with anti-HER2 antibodies, may represent a promising strategy in treating patients with gastric cancer with confirmed human epidermal growth factor receptor 2 (HER2) expression. The aim of the study was to synthesize a new 4-thiazolidinone derivative (Les-4367) and investigate its molecular mechanism of action in combination with trastuzumab or pertuzumab in human AGS gastric cancer cells. AGS cell viability and antiproliferative potential were examined. The effect of the tested combinations as well as monotherapy on apoptosis and autophagy was also determined. Metalloproteinase-2 (MMP-2), intercellular adhesion molecule 1 (ICAM-1), pro-inflammatory and anti-inflammatory cytokine concentrations were also demonstrated by the ELISA technique. We proved that pertuzumab and trastuzumab were very effective in increasing the sensitivity of AGS gastric cancer cells to novel Les-4367. The molecular mechanism of action of the tested combination is connected with the induction of apoptosis. Additionally, the anticancer activity is not associated with the autophagy process. Decreased concentrations of pro-inflammatory cytokines, MMP-2 and ICAM-1-were observed. The novel combination of drugs based on anti-HER2 antibodies with Les-4367 is a promising strategy against AGS gastric cancer cells.

摘要

将化疗与免疫疗法相结合仍然是癌症治疗的一种方案。新型含 4-噻唑烷酮的杂合分子具有良好的抗癌活性，与抗 HER2 抗体联合使用，可能是治疗 HER2 表达明确的胃癌患者的一种有前途的策略。本研究的目的是合成一种新型 4-噻唑烷酮衍生物（Les-4367），并研究其与曲妥珠单抗或帕妥珠单抗联合在人 AGS 胃癌细胞中的作用机制。检测了 AGS 细胞活力和抗增殖潜力。还测定了测试组合以及单药治疗对细胞凋亡和自噬的影响。还通过 ELISA 技术证明了金属蛋白酶-2（MMP-2）、细胞间黏附分子 1（ICAM-1）、促炎和抗炎细胞因子的浓度。我们证明了帕妥珠单抗和曲妥珠单抗非常有效地提高了 AGS 胃癌细胞对新型 Les-4367 的敏感性。测试组合的作用机制与诱导细胞凋亡有关。此外，抗癌活性与自噬过程无关。观察到促炎细胞因子、MMP-2 和 ICAM-1 的浓度降低。基于抗 HER2 抗体与 Les-4367 的新型药物联合是治疗 AGS 胃癌细胞的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/3d7db819caf5/ijms-24-06791-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/01915b2da016/ijms-24-06791-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/a76292f85f2f/ijms-24-06791-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/10dcd2ecfceb/ijms-24-06791-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/175cc9bae64a/ijms-24-06791-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/c7f302f8d6d8/ijms-24-06791-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/3d7db819caf5/ijms-24-06791-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/01915b2da016/ijms-24-06791-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/a76292f85f2f/ijms-24-06791-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/10dcd2ecfceb/ijms-24-06791-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/175cc9bae64a/ijms-24-06791-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/c7f302f8d6d8/ijms-24-06791-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbe9/10095353/3d7db819caf5/ijms-24-06791-g008.jpg

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2
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Korean J Gastroenterol. 2022 Apr 25;79(4):170-176. doi: 10.4166/kjg.2022.008.
3
2-{5-[(,2)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}-3-methylbutanoic Acid as a Potential Anti-Breast Cancer Molecule.
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Cancers (Basel). 2024 Aug 22;16(16):2924. doi: 10.3390/cancers16162924.
4
Role of Ciminalum-4-thiazolidinone Hybrids in Molecular NF-κB Dependent Pathways.Ciminalum-4-噻唑烷酮杂合体在分子 NF-κB 依赖途径中的作用。
Int J Mol Sci. 2024 Jul 3;25(13):7329. doi: 10.3390/ijms25137329.
2-{5-[(,2)-2-氯-3-(4-硝基苯基)-2-丙烯基]-4-氧代-2-噻唑烷-3-基}-3-甲基丁酸作为一种有潜力的抗乳腺癌分子。
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8
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10
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