索拉非尼联合脂质体阿霉素治疗甲状腺低分化癌裸鼠移植瘤的疗效观察

Effects of sorafenib and liposome doxorubicin on human poorly differentiated thyroid carcinoma xenografts in nude mice

目的评估索拉非尼、脂质体阿霉素及两者联合应用治疗甲状腺低分化癌裸鼠移植瘤的疗效。方法用脂质体阿霉素和索拉非尼治疗甲状腺低分化癌裸鼠皮下移植瘤模型，裸鼠按随机数字法分为7组，为空白对照组、溶剂对照组、单药脂质体阿霉素组、索拉非尼组、低剂量联合组、中剂量联合组和高剂量联合组，观察肿瘤生长情况，评估两种药物的疗效。结果利用索拉非尼和脂质体阿霉素对甲状腺低分化癌模型进行化疗，空白对照组、溶剂对照组、单药脂质体阿霉素组、索拉非尼组、低剂量联合组、中剂量联合组、高剂量联合组化疗结束后的最终肿瘤体积分别为（1274．13±393．76）mm3、（1060．00±469．05）mm3、（726．76±488．22）mm3、（451．54±97．75）mm3、（518．37±164．44）mm3、（310．51±210．53）mm3和（228．44±129．21）mm3，各组移植瘤最终瘤体质量分别为（1．13±0．42）g、（0．91±0．39）g、（0．78±0．45）g、（0．55±0．17）g、（0．52±0．19）g、（0．34±0．21）g和（0．194-0．09）g，单药脂质体阿霉素组、索拉非尼组、低剂量联合组、中剂量联合组、高剂量联合组的抑瘤率分别为30．8％、40．8％、42．3％、62．9％和72．6％，高剂量联合组抑瘤率除与中剂量联合组差异无统计学意义外（P=0．357）均高于其余各组，中剂量联合组优于单药脂质体阿霉素组（P；0．001），而与索拉非尼组差异无统计学意义（P=0．192）。各治疗组平均瘤体质量均明显低于空白对照组（F=9．985，P〈0．05）。各治疗组均无荷瘤鼠死亡，高剂量联合组荷瘤鼠体质量在治疗过程中较其余各治疗组有明显减轻（F=14．792，P〈0．05）。结论脂质体阿霉素和索拉非尼无论是单药还是联合应用对甲状腺低分化癌移植瘤模型均有明显的抑瘤作用，中剂量联合疗效明显且副作用小。

Objective To evaluate the therapeutic effects of sorafenib and liposome doxorubicin on poorly differentiated thyroid carcinoma （PDTC） xenografts in nude mice. Methods Sorafenib and liposome doxorubicin were applied to PDTC xenografts in nude mice. The mice were randomized into seven groups： blank control（ A）, vehicle control （B）, single liposome doxorubicin group （C）, single sorafenib group （D）, liposome doxorubicin combined with low dose sorafenib group（E） , combined group with medium dosage of sorafenib（F） , combined group with high-dose of sorafenib （G）. The volume, weight and growth inhibition rate of tumours were measured to evaluate the therapeutic effects of the drugs. Results Sorafenib and liposome doxorubicin showed significant antitumor activity in the PDTC xenografts. The mean tumor volumes of seven groups were （ 1274.13 ± 393.76 ）mm3, （ 1060.00 ± 469.05 ） mm3, （ 726.76 ± 488.22 ）mm3 , （451.54 ± 97.75 ） mm3, （518.37 ± 164.44） mm3, （310.51 ± 210.53 ） mm3, and （228.44 ± 129.21 ） mm3 , respectively. The mean tumor weights of the seven groups were （ 1.13 ± 0.42） g, （0.91 ± 0.39） g,（0.78 ±0.45）g, （0.55 ±0.17）g, （0.52 ±0.19）g, （0.34 ±0.21）g, and （0.19 ±0.09）g separately. The tumor inhibition rates of group C to G were 30.8% , 40.8% , 42.3% , 62.9% , 72.6% separately. Conclusions Sorafenib and liposome doxorubicin, no matter for single agent or in combination, showed significant antitumor activity in the PDTC PDTC xenografts in vivo. The tumour-inhibited effect of single sorafenib is better than that of single liposome doxorubiein. Liposome doxorubicin combined with medium dosage of sorafenib had a better therapeutic effect and less side effects.