Khosrawipour Carolina, Diakun Agata, Li Shiri, Lau Hien, Kulas Joanna, Khosrawipour Veria, Kielan Wojciech, Mikolajczyk-Martinez Agata
Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.
2nd Department of General Surgery and Surgical Oncology, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Pharmaceuticals (Basel). 2023 May 18;16(5):763. doi: 10.3390/ph16050763.
A newly introduced combination of intraperitoneal dehydration and hyperthermia has recently been shown to be feasible and cytotoxic for colon cancer cells in vivo. For the first time, our study now aims to evaluate dehydration under hyperthermic conditions combined with chemotherapy for potential use in the clinical setting. In this study, in vitro colon cancer cells (HT-29) were subjected to single or several cycles of partial dehydration under hyperthermic conditions (45 °C), followed by chemotherapy (triple exposure) with oxaliplatin or doxorubicin in various configurations. The viability, cytotoxicity, and proliferation of cells after the proposed protocols were assessed. Intracellular doxorubicin uptake was measured via flow cytometry. After one cycle of triple exposure, the viability of HT-29 cells was significantly reduced versus the untreated control (65.11 ± 5%, < 0.0001) and versus only chemotherapy (61.2 ± 7%, < 0.0001). An increased chemotherapeutic inflow into the cells after triple exposure was detected (53.4 ± 11%) when compared to cells treated with chemotherapy alone (34.23 ± 10%) ( < 0.001). Partial dehydration in a hyperthermic condition combined with chemotherapy increases the overall cytotoxicity of colon cancer cells significantly compared to chemotherapy alone. This could possibly be related to enhanced intracellular uptake of chemotherapeutic agents after partial dehydration. Further studies are required for the further evaluation of this new concept.
最近引入的腹腔内脱水和热疗联合疗法已被证明在体内对结肠癌细胞是可行的且具有细胞毒性。我们的研究首次旨在评估热疗条件下的脱水与化疗联合使用在临床环境中的潜在应用。在本研究中，体外结肠癌细胞（HT-29）在热疗条件（45°C）下经历单周期或多周期的部分脱水，随后用奥沙利铂或多柔比星以各种组合进行化疗（三联暴露）。评估了所提出方案后细胞的活力、细胞毒性和增殖情况。通过流式细胞术测量细胞内多柔比星的摄取量。三联暴露一个周期后，HT-29细胞的活力与未处理的对照相比显著降低（65.11±5%，<0.0001），与仅化疗相比也显著降低（61.2±7%，<0.0001）。与单独接受化疗的细胞（34.23±10%）相比，三联暴露后检测到细胞内化疗药物流入增加（53.4±11%）（<0.001）。与单独化疗相比，热疗条件下的部分脱水与化疗联合使用可显著提高结肠癌细胞的总体细胞毒性。这可能与部分脱水后化疗药物的细胞内摄取增加有关。需要进一步研究以进一步评估这一新概念。
