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紫杉醇或多西紫杉醇腹腔化疗治疗卵巢癌时的发热:有何获益?

Hyperthermia During Intraperitoneal Chemotherapy With Paclitaxel or Docetaxel for Ovarian Cancer: Is There Any Benefit?

机构信息

Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece;

Department of Biochemistry, Medical School of Crete, Heraklion, Greece.

出版信息

Anticancer Res. 2020 Dec;40(12):6769-6780. doi: 10.21873/anticanres.14700. Epub 2020 Dec 7.

Abstract

BACKGROUND/AIM: Intraperitoneal chemotherapy with taxanes provides high locoregional drug concentrations. Regarding their synergy with hyperthermia, results have been inconclusive. In this in vitro study, the thermal enhancement of the effect of paclitaxel and docetaxel on ovarian cancer cells under conditions mimicking those during hyperthermic intraperitoneal chemotherapy (HIPEC) is evaluated.

MATERIALS AND METHODS

Cisplatin-resistant SKOV-3 and OVCAR-3 ovarian cancer cells were exposed for 2 h to 0.1, 1 and 3 μΜ of paclitaxel and docetaxel at 37°C (normothermia) and 41.5°C (hyperthermia). Cell proliferation and cell-cycle distribution were evaluated after 24 h, 3 days and 7 days.

RESULTS

A concentration-dependent cytotoxic effect on cell proliferation was observed. Concurrent hyperthermia caused an increased arrest of cells in the G/M phase. At 7 days, thermal enhancement of drug effect was shown only for treatment of OVCAR-3 cells with 1 μM paclitaxel.

CONCLUSION

The concentration-dependent cytotoxic effect of paclitaxel and docetaxel supports their intraperitoneal use. Due to the lack of or only minimal thermal enhancement, normothermic may be as effective as hyperthermic intraoperative intraperitoneal chemotherapy with taxanes, avoiding, however, potential oncological and treatment-related adverse effects of concurrent hyperthermia.

摘要

背景/目的:紫杉醇腹腔化疗可使局部药物浓度升高。关于其与热疗的协同作用,结果尚无定论。本体外研究旨在评估在模拟腹腔热灌注化疗(HIPEC)条件下紫杉醇和多西他赛对卵巢癌细胞的热增强作用。

材料和方法

将顺铂耐药的 SKOV-3 和 OVCAR-3 卵巢癌细胞在 37°C(常温)和 41.5°C(热疗)下分别暴露于 0.1、1 和 3 μM 的紫杉醇和多西他赛 2 小时。在 24 小时、3 天和 7 天后评估细胞增殖和细胞周期分布。

结果

观察到细胞增殖的浓度依赖性细胞毒性作用。同时热疗导致细胞更多地停滞在 G2/M 期。在第 7 天,仅在 1 μM 紫杉醇处理 OVCAR-3 细胞时显示出药物作用的热增强。

结论

紫杉醇和多西他赛的浓度依赖性细胞毒性作用支持其腹腔内使用。由于缺乏或仅轻微的热增强作用,常温下可能与紫杉醇的术中腹腔内热灌注化疗一样有效,同时避免了同时热疗的潜在肿瘤学和治疗相关不良影响。

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