钙细胞毒性使前列腺癌细胞对局部晚期肿瘤的标准治疗更敏感。
Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors.
机构信息
Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
Department of Science and Technology (DST), University of Sannio, Benevento, Italy.
出版信息
Cell Death Dis. 2020 Dec 7;11(12):1039. doi: 10.1038/s41419-020-03256-5.
Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca cytotoxicity is an actionable strategy to sensitize cancer cells to standard therapies.
治疗抵抗是肿瘤学的主要障碍。加剧癌细胞典型的分子功能障碍已被证明能有效地扭转致癌机制，使其达到致命状态，从而为癌症治疗提供新的治疗途径。在这里，我们证明了瞬时受体电位阳离子通道亚家族 M 成员 8（TRPM8）的选择性激动剂，一种前列腺上皮细胞的阳离子通道，在晚期 III/IV 期前列腺癌（PCa）中经常过表达，能使 PCa 的治疗抵抗模型对放疗、化疗或激素治疗敏感。总的来说，我们的研究表明，药理诱导的 Ca 细胞毒性是一种使癌细胞对标准治疗敏感的可行策略。
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