腹腔热化疗中卵巢癌细胞对顺铂敏感性影响的体外研究

Hyperthermia and Cisplatin Sensitivity of Ovarian Cancer and Its Mechanism in vitro

  • 摘要: 目的:探讨腹腔热疗对卵巢癌细胞顺铂敏感株的化疗增敏作用及对顺铂耐药株的逆转耐药作用,并分析其作用机制,为腹腔热疗增加顺铂化疗敏感性及逆转卵巢癌顺铂耐药提供实验依据。方法:MTT 法研究常温及41℃不同作用时间下温热联合顺铂对卵巢癌细胞敏感株SKOV 3、卵巢癌细胞顺铂耐药株SKOV 3/DDP 的生长抑制作用。Western bloting法检测常温及41℃不同作用时间下ERCC1 基因表达水平。结果:41℃下作用60、90min时对SKOV 3 细胞生长的抑制作用大,差异有显著性,P<0.001。热处理对SKOV 3/DDP 细胞生长有抑制作用,不同时间差异有统计学意义。热疗联合顺铂在常温或41℃下,SKOV 3 细胞对顺铂的敏感性不同,差异有统计学意义(P<0.001)。 且41℃作用90min时敏感性最大(P=0.002),对顺铂的敏感性提高79.885% 。热处理不同时间,SKOV 3/DDP 细胞对顺铂的敏感性增加,差异有显著性,P<0.001。41℃90min SKOV3/DDP 细胞对顺铂的敏感性提高37.129% 。在SKOV 3 细胞中,ERCC1 表达水平较SKOV 3/DDP 细胞降低,F=32.175,P<0.001。热疗联合顺铂与常温下相比,SKOV 3、SKOV 3/DDP 细胞中ERCC1 基因表达水平差异无统计学意义,F=0.962,P=0.443。结论:热疗对卵巢癌细胞SKOV 3 及其顺铂耐药亚株SKOV 3/DDP 细胞有生长抑制作用;热疗联合顺铂可以增加SKOV 3 细胞对顺铂的敏感性,可以部分逆转SKOV 3/DDP细胞对顺铂的耐药性,且最佳作用时间为41℃90min;ERCC1 表达增加与卵巢癌顺铂耐药有关,但热疗联合顺铂对ERCC1 基因表达水平无明显影响,热疗可能通过其他途径增加肿瘤细胞对顺铂的敏感性。

     

    Abstract: Objective: Our purpose is to study whether hyperthermia combined with cisplatin enhances drug sensitivity and reverses drug resistance in ovarian cancer cell lines. Methods:MTT was used to study the cell proliferation and inhibi-tion rates in SKOV 3 and cisplatin-resistant SKOV 3/DDP cells. We estimated the expression of the ERCC 1 gene in SKOV3 and SKOV 3/DDP cells by Western blotting to analyze the mechanism of hyperthermia combined with cisplatin. Results: ① At less than 41℃for 90min and 120 min, the inhibitory effects of cisplatin on SKOV3 cells are statistically significant ( P< 0.001 ). At less than 41℃at various times, the inhibitory effects of cisplatin on SKOV3/DDP cells are statistically significant (F=18.135 , P<0.001 ). ②Comparing the hyperthermic effect of cisplatin at room temperature and at41℃at various times, the sensitivity of cisplatin on SKOV 3 cells was significantly different (F=67.489 , P<0.001 ). At 41℃and 90min the sensitivity was higher than at60min (P=0.002 ). The sensitivity to cisplatin by SKOV 3 cells was increased 79.885 %, and the sensitivity to cisplatin on SKOV3/DDP cells was significantly different ( F=18.356 , P<0.001 ). The sensitivity of cisplatin on SKOV 3/DDP cells was increased 37.129 %. The sensitivity to cisplatin was higher at41℃than at room temperature. ③The expression of the ERCC 1 gene in SKOV3 was significantly lower than in SKOV3/DDP (F=32.175 , P<. 001 ), but there was no difference in expression of ERCC 1 in SKOV 3 and SKOV 3/DDP cells between room temperature and 41℃(30min, 60min, 90min and 120 min) (F=0.962 , P=0.443 ). Conclusion : Thermotherapy has an inhibitory effect on SKOV 3 and SKOV 3/DDP cells. Ther -motherapy increased the sensitivity of SKOV3 cells to cisplatin and reversed the drug-resistance of SKOV 3/DDP. The opti -mal experimental conditions were 41℃and 90min. The expression of ERCC1 in SKOV 3 cells was lower than SKOV3/DDP cells, but there was no difference between the cells at room temperature and the four time points at 41℃in either SKOV 3 or SKOV3/DDP cells. Hyperthermia increases the sensitivity of SKOV 3 to cisplatin and reverses the drug-resistance of SKOV 3/DDP.

     

/

返回文章
返回