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首页> 外文期刊>BJU international >Cryoablative response of prostate cancer cells is influenced by androgen receptor expression.
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Cryoablative response of prostate cancer cells is influenced by androgen receptor expression.

机译：前列腺癌细胞的冷冻反应受雄激素受体表达的影响。

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OBJECTIVE: To investigate in prostate cancer cells the consequences of androgen-insensitivity (AI) development on the cellular and molecular responses to freezing, as a challenge in prostate cancer treatment occurs when the androgen-sensitive (AS) phenotype switches to an AI phenotype, the latter of which is often refractory to many therapies. MATERIALS AND METHODS: PC-3 (AI) and LNCaP (AS) were each genetically altered to express the opposite phenotype and subjected to an in vitro freezing model. Viability, caspase inhibitor and Western blot studies were used to determine the basis of the differential responses of AI and AS cells. RESULTS: LNCaP high-passage cells, formed by repeated passage of LNCaP (AS) cells, were AI and showed a phenotypic shift to freeze resistance matching the freeze response of PC-3 cells (AI). While stably transfected androgen receptor (AR)-transfected cells (PC-3 AR) had a freezing sensitivity similar to that of the LNCaP (AS) cell line. Importantly, AI cell lines survived and recovered from freezing exposure to temperatures as low as -40 degrees C whereas AS cell lines did not. Caspase inhibition studies and related fluorescent probes showed an elevated level of apoptotic involvement in both AS cell lines after freezing compared with their AI counterparts. Western blot analysis showed that AR expression was modified after exposure to freezing. CONCLUSION: This study suggests that AS cancers may be far more sensitive to a freezing insult and this might be linked to elevated apoptosis and caspase activity. As such, cryoablation may prove most effective in cancer cells that have not yet progressed to a more resistant AI phenotype, but both generic variants can be fully ablated at sufficiently low temperatures.
机译：目的：研究在前列腺癌细胞中雄激素不敏感性（AI）发展对细胞和分子对冰冻反应的后果，因为当雄激素敏感性（AS）表型转换为AI表型时，前列腺癌治疗面临挑战，后者常常使许多疗法难治。材料与方法：对PC-3（AI）和LNCaP（AS）进行了遗传改造，以表达相反的表型，并进行了体外冷冻模型。生存力，caspase抑制剂和蛋白质印迹研究被用来确定AI和AS细胞差异反应的基础。结果：通过反复传代LNCaP（AS）细胞而形成的LNCaP高传代细胞为AI，表现出与PC-3细胞（AI）的冷冻反应相匹配的向抗冻性的表型转变。稳定转染的雄激素受体（AR）转染的细胞（PC-3 AR）具有与LNCaP（AS）细胞系相似的冷冻敏感性。重要的是，AI细胞系可以通过冷冻暴露于低至-40摄氏度的温度来生存和恢复，而AS细胞系则不能。 Caspase抑制研究和相关的荧光探针显示，与AI对应物相比，冷冻后两种AS细胞系的凋亡参与水平均升高。蛋白质印迹分析表明，暴露于冰冻后，AR表达被修饰。结论：这项研究表明，AS癌症可能对冷冻损伤更为敏感，这可能与细胞凋亡和胱天蛋白酶活性升高有关。因此，冷冻消融可能在尚未发展为更具抗性的AI表型的癌细胞中被证明是最有效的，但是两种通用变体都可以在足够低的温度下完全消融。

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