■结直肠癌(CRC)的腹膜转移是一个重要的临床挑战,预后不良,通常对全身化疗无反应。细胞减灭术(CRS)联合腹腔热化疗(HIPEC)是一种针对特定患者的治疗方法。姜黄素的使用,一种具有抗肿瘤特性的天然化合物,HIPEC中的药物由于其与常规药物相比具有较低的副作用以及通过直接递送至腹膜腔增加功效的潜力而受到关注。
■开发了体外高温模型以模拟临床HIPEC条件。三种结肠癌细胞系(SK-CO-1,COLO205,SNU-C1)代表不同的基因突变(p53,KRAS,BRAF)用姜黄素(25µM)或丝裂霉素-C(1µM)处理1、2或3小时。后处理,将细胞在37°C(正常体温)或42°C(高温)下孵育。使用膜联蛋白V/PI在治疗后24、48和72小时评估细胞活力和增殖。MTT测定,锥虫蓝排除,和霍夫曼显微镜。
■热疗可显著增强姜黄素的抗肿瘤功效,与所有细胞系的正常体温相比,细胞活力降低了两倍。在SNU-C1细胞系中,带有p53突变,丝裂霉素C未能显著影响细胞活力,不像姜黄素,提示治疗反应的突变特异性差异。
■研究结果表明,热疗可增强姜黄素的体外抗肿瘤作用,支持姜黄素可能是比丝裂霉素-C等传统药物更有效的HIPEC药物的假说。观察到与突变相关的差异对治疗的反应,特别是在p53突变细胞中。虽然还需要进一步的研究,这些初步结果提示,姜黄素在HIPEC中可能成为CRC腹膜转移患者的一种新的治疗策略.这种方法可以提供更好的结果,副作用更少,特别是在遗传上不同的CRC亚型中。
UNASSIGNED: Peritoneal metastases from colorectal cancer (CRC) present a significant clinical challenge with poor prognosis, often unresponsive to systemic chemotherapy. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment approach for select patients. The use of curcumin, a natural compound with antitumor properties, in HIPEC is of interest due to its lower side effects compared to conventional drugs and potential for increased efficacy through direct delivery to the peritoneal cavity.
UNASSIGNED: An in vitro hyperthermic model was developed to simulate clinical HIPEC conditions. Three colon cancer cell lines (SK-CO-1, COLO205, SNU-C1) representing different genetic mutations (p53, KRAS, BRAF) were treated with either curcumin (25 µM) or mitomycin-C (1 µM) for 1, 2, or 3 hours. Post-treatment, cells were incubated at 37°C (normothermia) or 42°C (hyperthermia). Cell viability and proliferation were assessed at 24, 48 and 72 hours post-treatment using Annexin V/PI, MTT assay, trypan blue exclusion, and Hoffman microscopy.
UNASSIGNED: Hyperthermia significantly enhanced the antitumor efficacy of curcumin, evidenced by a two-fold reduction in cell viability compared to normothermia across all cell lines. In the SNU-C1 cell line, which harbors a p53 mutation, mitomycin-C failed to significantly impact cell viability, unlike curcumin, suggesting mutation-specific differences in treatment response.
UNASSIGNED: The findings indicate that hyperthermia augments the antitumor effects of curcumin in vitro, supporting the hypothesis that curcumin could be a more effective HIPEC agent than traditional drugs like mitomycin-C. Mutation-associated differences in response to treatments were observed, particularly in p53 mutant cells. While further studies are needed, these preliminary results suggest that curcumin in HIPEC could represent a novel therapeutic strategy for CRC patients with peritoneal metastases. This approach may offer improved outcomes with fewer side effects, particularly in genetically distinct CRC subtypes.