顺铂和洛铂与放射联合对小鼠肺癌移植瘤生长的影响

目的 了解顺铂、洛铂给药后不同时间照射对小鼠肺癌移植瘤的放射增敏作用影响.方法 70只C57BL/6近交系Lewis肺癌移植小鼠随机分组,按10 mg药物/kg体重经尾静脉分别注射顺铂和洛铂,给药后在0.5、2.0、4.0、24.0、48.0、72.0、96.0 h分别将小鼠处死获取肿瘤组织标本,应用ICP-MS方法测定标本铂含量.80只荷瘤小鼠随机分为对照、单纯药物、单纯照射、药物联合照射组共10个组,注射药物后1、24 h或72 h对肿瘤局部进行照射,比较各组间肿瘤大小.结果 顺铂、洛铂在肿瘤组织浓度均在给药后迅速达到4.78、2.79 μg/g (t=3.82,P=0.005),4 h后分别降至3.39、0.99 μg/g (t=9.10,P=0.000),96 h时分别为1.41、0.23 μg/g (t=3.70,P=0.006).顺铂给药后1、24、72 h照射组之间肿瘤生长速度相似,但比对照组、单纯照射组、单纯顺铂组均明显变缓;在第15天时肿瘤相对体积分别为4.73、5.52、2.15(F=0.84,P=0.451),而对照组、单纯照射组、单纯顺铂组分别为16.63(F=10.50,P=0.000)、10.34(F=3.12,P=0.046)、12.80(F=8.06,P=0.001).洛铂给药后1、24、72 h照射组之间肿瘤生长速度也相似,但与对照组、单纯照射组、单纯洛铂组相比均明显变缓;在第15天时肿瘤相对体积分别为3.49、4.90、3.86(F=0.32,P=0.727),而对照组、单纯照射组、单纯洛铂组分别为16.63(F=15.21,P=0.000)、10.34(F=4.12,P=0.016)、14.28(F=10.67,P=0.000).顺铂和洛铂在1、24、72 h的放射增敏比分别为2.13、2.03、3.45和2.53、2.00、2.50.结论 顺铂一次给药后肿瘤内药物浓度至少能持续96 h,其放射增敏作用能持续较长时间;洛铂具有与顺铂相似的抗肿瘤效果及放射增敏作用.

Abstract：

Objective To learn the effect of different combination model between irradiation and cisplatin or lobaplatin on the radiosensitization of xenographt tumor in mice.Methods Seventy C57BL/6 mice with Lewis lung carcinoma were randomly divided into fourteen groups.Then a single intravenous bolus injection of 10 mg/kg either cisplatin or lobaplatin was given.Tumor tissues were collected at the indicated times of 0.5 h, 2.0 h, 4.0 h, 24.0 h, 48.0 h, 72.0 h, and 96.0 h.The platinum levels were determined by inductively coupled plasma-mass spectrometry.Eighty tumor-bearing mice were randomly divided into 10 groups, including a blank control group, a irradiation group, two drug treatment groups and 6 combined treatment groups.The tumors were irradiated at 1 h, 24 h or 72 h after either cisplatin or lobaplatin injection.The tumor size of the groups was compared.Results The concentrations of cisplatin and lobaplatin in tumors rapidly reached 4.78 μg/g and 2.79 μg/g (t=3.82,P=0.005), respectively, then declined rapidly to 3.39 μg/g and 0.99 μg/g (t=9.10,P=0.000) at 4 h, 1.41 μg/g and 0.23 μg/g (t=3.70,P=0.006) at 96 h, respectively.The tumor growth among the three groups of irradiation at 1 h, 24 h or 72 h after cisplatin was similar, which was slower than the blank control group, the irradiation group and the cisplatin treatment group.At the 15th day, the relative volume of tumor in the three combined treatment groups were 4.73, 5.52 and 2.15(F=0.84,P=0.451), While was 16.63(F=10.50,P=0.000) in the blank control group, 10.34(F=3.12,P=0.046) in the irradiation group, and 12.80(F=8.06,P=0.001) in the cisplatin treatment group, respectively.The tumor growth among the three groups of irradiation at 1 h, 24 h or 72 h after lobaplatin was also similar, which was slower than the blank control group, the irradiation group and the lobaplatin treatment group.At the 15th day, the relative volume of tumor in the three combined treatment groups were 3.49, 4.90 and 3.86(F=0.32,P=0.727), While was 16.63(F=15.21,P=0.000) in the blank control group, 10.34(F=4.12,P=0.016) in the irradiation group, and 14.28(F=10.67,P=0.000) in the lobaplatin treatment group, respectively.The sensitizing enhancement ratio (SER) at 1 h, 24 h and 72 h after the injection were 2.13, 2.03 and 3.45 of cisplatin, and 2.53, 2.00 and 2.50 of lobaplatin, respectively.Conclusions After intravenous bolus injection, the cisplatin concentration in the tumor can be kept at least 96 hours, which results in a persistent radiosensitizing effect.Lobaplatin and cisplatin have similar anti-tumor and radiosensitizing effect.

The effect of different combinations between irradiation and cisplatin or lobaplatin on tumor growth in mice

Objective To learn the effect of different combination model between irradiation and cisplatin or lobaplatin on the radiosensitization of xenographt tumor in mice.Methods Seventy C57BL/6 mice with Lewis lung carcinoma were randomly divided into fourteen groups.Then a single intravenous bolus injection of 10 mg/kg either cisplatin or lobaplatin was given.Tumor tissues were collected at the indicated times of 0.5 h, 2.0 h, 4.0 h, 24.0 h, 48.0 h, 72.0 h, and 96.0 h.The platinum levels were determined by inductively coupled plasma-mass spectrometry.Eighty tumor-bearing mice were randomly divided into 10 groups, including a blank control group, a irradiation group, two drug treatment groups and 6 combined treatment groups.The tumors were irradiated at 1 h, 24 h or 72 h after either cisplatin or lobaplatin injection.The tumor size of the groups was compared.Results The concentrations of cisplatin and lobaplatin in tumors rapidly reached 4.78 μg/g and 2.79 μg/g (t=3.82,P=0.005), respectively, then declined rapidly to 3.39 μg/g and 0.99 μg/g (t=9.10,P=0.000) at 4 h, 1.41 μg/g and 0.23 μg/g (t=3.70,P=0.006) at 96 h, respectively.The tumor growth among the three groups of irradiation at 1 h, 24 h or 72 h after cisplatin was similar, which was slower than the blank control group, the irradiation group and the cisplatin treatment group.At the 15th day, the relative volume of tumor in the three combined treatment groups were 4.73, 5.52 and 2.15(F=0.84,P=0.451), While was 16.63(F=10.50,P=0.000) in the blank control group, 10.34(F=3.12,P=0.046) in the irradiation group, and 12.80(F=8.06,P=0.001) in the cisplatin treatment group, respectively.The tumor growth among the three groups of irradiation at 1 h, 24 h or 72 h after lobaplatin was also similar, which was slower than the blank control group, the irradiation group and the lobaplatin treatment group.At the 15th day, the relative volume of tumor in the three combined treatment groups were 3.49, 4.90 and 3.86(F=0.32,P=0.727), While was 16.63(F=15.21,P=0.000) in the blank control group, 10.34(F=4.12,P=0.016) in the irradiation group, and 14.28(F=10.67,P=0.000) in the lobaplatin treatment group, respectively.The sensitizing enhancement ratio (SER) at 1 h, 24 h and 72 h after the injection were 2.13, 2.03 and 3.45 of cisplatin, and 2.53, 2.00 and 2.50 of lobaplatin, respectively.Conclusions After intravenous bolus injection, the cisplatin concentration in the tumor can be kept at least 96 hours, which results in a persistent radiosensitizing effect.Lobaplatin and cisplatin have similar anti-tumor and radiosensitizing effect.