甲磺酸阿帕替尼治疗肾透明细胞癌的实验和临床研究

Experimental and Clinical Study of Apatinib Mesylate in the Treatment of Clear Cell Renal Cell Carcinoma

目的探讨甲磺酸阿帕替尼对人肾透明细胞癌786-O细胞在裸鼠皮下移植瘤生长中的抑制作用,并回顾分析2018年1月—2019年9月甲磺酸阿帕替尼治疗晚期肾癌的疗效及安全性。方法将体外培养的人肾透明细胞癌786-O细胞接种于裸鼠皮下,建立移植瘤模型,随机分为对照组(生理盐水组)及甲磺酸阿帕替尼低剂量组(50 mg/kg)、中剂量组(100 mg/kg)和高剂量组(200 mg/kg),每组6只,灌胃连续治疗14 d,治疗过程中测量肿瘤的质量和体积,观察各组移植瘤组织血管生成和增殖情况。观察32例晚期肾癌患者接受甲磺酸阿帕替尼治疗效果及安全性。结果治疗2周后,与对照组相比,甲磺酸阿帕替尼中、高剂量组裸鼠移植瘤体积缩小、质量下降,CD34和Ki-67蛋白表达水平降低(P<0.05)。32例晚期肾癌患者疾病控制率为81.2%,客观缓解率为28.1%。不良反应大部分为1~2级,3级以上不良反应可通过停药或减量缓解症状。结论甲磺酸阿帕替尼对肾癌裸鼠移植瘤具有抑制作用,可能与抑制肿瘤血管生成及增殖有关,同时临床研究提示,甲磺酸阿帕替尼可有效控制疾病进展,多数不良反应可耐受。

Objective To investigate the inhibitory effect of Apatinib Mesylate on the growth of human clear cell renal cell carcinoma(CCRCC)786-O cells in subcutaneously transplanted tumor in nude mice,and to retrospectively analyze the clinical efficacy and safety of apatinib mesylate in the treatment of patients with advanced renal cancer from January 2018 to September 2019.Methods Human CCRCC 786-O cells cultured in vitro were inoculated subcutaneously in nude mice to establish the transplanted tumor model.They were randomly divided into control group(normal saline group),low-dose Apatinib Mesylate group(50 mg/kg,n=6),medium-dose Apatinib Mesylate group(100 mg/kg,n=6)and high-dose Apatinib Mesylate group(200 mg/kg,n=6).They were treated by gavage for 14 d.The mass and volume of the tumor were measured during the treatment,and the angiogenesis and proliferation of transplanted tumor tissues in each group were observed.The efficacy and safety of 32 patients with advanced renal cell carcinoma treated with apatinib mesylate were observed.Results At 2 weeks after treatment,the volume and quality of transplanted tumor in nude mice in medium and high-dose apatinib mesylate groups decreased and the tumor inhibition rate increased,as compared with the control group,and protein expressions of CD34 and Ki-67 were significantly lower(P<0.05).The disease control rate of 32 patients with advanced renal cell carcinoma was 81.2%,and the objective remission rate was 28.1%.Most of the adverse reactions were grade 1-2,and adverse reactions above grade 3 could be relieved by drug withdrawal or dose reduction.Conclusion Apatinib mesylate has an inhibitory effect on transplanted tumor of renal carcinoma in nude mice,and its mechanism may be related to inhibiting tumor angiogenesis and proliferation.Meanwhile,clinical studies showed that apatinib mesylate can effectively control the progression of the disease,and most of the adverse reactions can be tolerated.