Raaphorst G P, Maio J, Ng C E, Stewart D J
Ottawa Regional Cancer Center, Ottawa, Ontario K1H 8L6, Canada.
Oncol Rep. 1998 Jul-Aug;5(4):971-7. doi: 10.3892/or.5.4.971.
Hyperthermia has been shown to be an effective radiation sensitizer. Cisplatin has also been shown to cause radiosensitization. In part, the sensitization is through the inhibition of repair of radiation damage. In this study we have set out to combine low dose-rate irradiation (during which extensive repair occurs) with both cisplatin and hyperthermia to maximize the radiation sensitizing effect. Two human ovarian carcinoma cell lines, one parental (A2780S) and the other a cisplatin resistant derivative (A2780CP) cell line were used in these experiments. Long duration hyperthermia at 40 degrees C was combined with low concentrations of cisplatin (0.5-3 microg/ml) and low dose-rate irradiation (LDRI). The responses to the individual treatments showed that there was cross resistance in the two cell lines for cisplatin and radiation, but for hyperthermia the opposite effect was found. When all treatments were given concurrently the response was greater than the calculated response of all three individual treatments, indicating a synergistic interaction. The effect was greater in the cisplatin resistant cell line. The combination of mild hyperthermia, low dose cisplatin and LDRI are a good combination for potential clinical application. In addition, this could be a good approach to deal with cisplatin resistance.
高温已被证明是一种有效的辐射增敏剂。顺铂也已被证明会引起放射增敏作用。部分增敏作用是通过抑制辐射损伤的修复来实现的。在本研究中，我们着手将低剂量率照射（在此期间会发生广泛的修复）与顺铂和高温相结合，以最大化辐射增敏效果。在这些实验中使用了两种人卵巢癌细胞系，一种是亲本细胞系（A2780S），另一种是顺铂耐药衍生细胞系（A2780CP）。40摄氏度的长时间高温与低浓度顺铂（0.5 - 3微克/毫升）和低剂量率照射（LDRI）相结合。对各个治疗的反应表明，这两种细胞系对顺铂和辐射存在交叉耐药性，但对高温则发现了相反的效果。当同时给予所有治疗时，反应大于三种单独治疗的计算反应，表明存在协同相互作用。在顺铂耐药细胞系中效果更明显。轻度高温、低剂量顺铂和LDRI的联合是潜在临床应用的良好组合。此外，这可能是应对顺铂耐药性的一种好方法。
