Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.
Cancer Med. 2020 May;9(10):3344-3352. doi: 10.1002/cam4.2941. Epub 2020 Mar 17.
Anlotinib is a novel, orally administered, multitarget receptor tyrosine kinase inhibitor. It functions by inhibiting tumor angiogenesis and proliferative signaling pathways. In this study, we aimed to investigate the efficacy and safety of anlotinib plus epirubicin in a sarcoma patient-derived xenografts (PDX) model.
We firstly established a PDX model using fresh tumor tissues that were surgically removed from a patient diagnosed with malignant fibrous histiocytoma. Thirty-six PDX models were divided into six groups and treated with anlotinib alone (low-dose, 1.5 or high-dose, 3.0 mg/kg/day, oral gavage), or with anlotinib plus epirubicin (3.0 mg/kg/once weekly, i.p.) when the tumors grew to 150-200 mm . After 5 weeks of treatment, the mice were sacrificed, and the tumors were measured by weight and processed for IHC and H&E staining. IHC staining was performed to detect CD31, EGFR, MVD, and Ki-67 on paraffin sections. H&E stainings were performed to examine the microcosmic changes that occurred in the tumor tissues and myocardium, respectively.
After 5 weeks, treatment with anlotinib or epirubicin alone significantly inhibited tumor growth in the sarcoma PDX model compared with the vehicle control. Tumor volume in the high-dose anlotinib group was significantly smaller than the low-dose anlotinib group (P < .001). Combined high-dose anlotinib and epirubicin treatment resulted in the most pronounced tumor inhibition. In the groups treated with the anlotinib-containing regimen, the expression levels of CD31, EGFR, MVD, and Ki-67 were significantly low. The weight in each group had no statistical differences; the same applied to the hepatic function, cardiac function, and toxicity.
High-dose anlotinib combined with epirubicin was an effective and safe therapy for STS.
安罗替尼是一种新型的、口服的、多靶点受体酪氨酸激酶抑制剂。它通过抑制肿瘤血管生成和增殖信号通路发挥作用。在这项研究中，我们旨在研究安罗替尼联合表柔比星在肉瘤患者来源异种移植（PDX）模型中的疗效和安全性。
我们首先使用从诊断为恶性纤维组织细胞瘤的患者手术切除的新鲜肿瘤组织建立 PDX 模型。36 个 PDX 模型分为 6 组，分别给予安罗替尼单药治疗（低剂量 1.5 或高剂量 3.0mg/kg/天，口服灌胃），或当肿瘤生长至 150-200mm3 时给予安罗替尼联合表柔比星治疗（3.0mg/kg/周一次，腹腔注射）。治疗 5 周后，处死小鼠，称重肿瘤，并进行免疫组织化学（IHC）和 H&E 染色。对石蜡切片进行 IHC 染色以检测 CD31、EGFR、MVD 和 Ki-67。分别对肿瘤组织和心肌组织进行 H&E 染色以检查微观变化。
5 周后，与对照组相比，安罗替尼或表柔比星单药治疗明显抑制了肉瘤 PDX 模型中的肿瘤生长。高剂量安罗替尼组的肿瘤体积明显小于低剂量安罗替尼组（P<0.001）。高剂量安罗替尼联合表柔比星治疗导致肿瘤抑制最显著。在接受含安罗替尼方案治疗的组中，CD31、EGFR、MVD 和 Ki-67 的表达水平明显降低。每组的体重均无统计学差异；肝功能、心功能和毒性也相同。
高剂量安罗替尼联合表柔比星是治疗 STS 的有效且安全的治疗方法。
