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Taxol is the first-line drug for cancer treatment. However, tumor resistance to Taxol is still a significant challenge in clinical practice. Here, we studied the synergistic effect of a ruthenium (II) polypyridyl complex, Δ-[Ru(bpy)2(HPIP)](ClO4)2(Δ-Ru1, where bpy = 2,2'-bipyridine, HPIP = 2-(2-hydroxyphenyl) imidazo[4,5-f] [1, 10] phenanthroline) combined with Taxol (Δ-Ru1 & Taxol) on Taxol resistant cervical cancer HeLa cell line (HeLa/Taxol). The results of the Chou-Talalay and Synergyfinder analytical test show that the Δ-Ru1 & Taxol combination has a synergistic effect in HeLa/Taxol cells. Especially, vesicles structures were observed on the membranes of HeLa/Taxol cells treated with Δ-Ru1 & Taxol, accompanied by cell swelling, which characterizes pyroptosis. Furthermore, the release of Interleukin-1β (IL-1β) and Lactate Dehydrogenase (LDH) were increased. At the same time, the activation and cleavage of Caspase-1 and Gasdermin D (GSDMD), the key molecules of the pyroptosis pathway, were detected. In addition, the Δ-Ru1 & Taxol combination had a synergistic anti-tumor effect in the mice model and could effectively inhibit tumor growth and significantly reduce the side effects on the lungs and the neuroethology of Taxol. Taken together, the Δ-Ru1 & Taxol combination can induce cell death through Caspase-1/GSDMD-mediated pyroptosis to enhance the therapeutic effect on HeLa/Taxol cells. This study provides a novel idea for the combined application of ruthenium complexes and other drugs, which may be utilized to overcome cancer drug resistance. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Dan Chen, Shunwen Guo, Xingguo Tang, Yi Rong, Huaben Bo, Han Shen, Zizhuo Zhao, Aimin Qiao, Juan Shen, Jinquan Wang. Combination of ruthenium (II) polypyridyl complex Δ-Ru1 and Taxol enhances the anti-cancer effect on Taxol-resistant cancer cells through Caspase-1/GSDMD-mediated pyroptosis. Journal of inorganic biochemistry. 2022 May;230:111749

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PMID: 35144218

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