Antitumor Effects of Apatinib on Tongue Cancer in Patient-Derived Xenograft Models.

[BACKGROUND] Tongue cancer is the most common malignant tumor in the oral and maxillofacial region. Novel effective therapies are urgently needed. Apatinib, a small-molecule antiangiogenic tyrosine kinase inhibitor, has demonstrated efficacy in gastric cancer, but its role in tongue cancer remains unclear. This study evaluated the antitumor effects and mechanisms of apatinib using patient-derived xenograft (PDX) models of tongue cancer.

[METHODS] Fresh tumor tissues from two tongue cancer patients (Affiliated Stomatological Hospital of Nanchang University, 2019-2021) were subcutaneously inoculated into immunodeficient mice to establish PDX models, validated by histology and human-specific gene identification. Eighteen P4-generation PDX mice were randomized into three groups (*n*=6/group): Control: 100 μL/day saline (oral gavage), Cisplatin: 5 mg/Kg/week (intraperitoneal injection), Apatinib: 100 mg/Kg/day (oral gavage). After 21 days of treatment, tumor volume/weight was measured. Immunohistochemistry (IHC) assessed microvessel density (MVD, via CD31) and cell proliferation (Ki-67). Data were analyzed by one-way ANOVA with Tukey's test.

[RESULTS] Apatinib significantly inhibited tumor growth, reducing tumor weight (0.21±0.07 g vs. Control 0.93±0.30 g, P=0.036) and volume (211.32±166.38 mm vs. Control 800.98±581.05 mm, P=0.0002). IHC revealed decreased MVD (0.88±0.07 vs. Control 4.30±0.34, P=0.0192) and Ki-67-positive cells (2.75%±0.28% vs. Control 32.05%±4.34%, P=0.047), indicating suppressed angiogenesis and proliferation. Mouse body weight remained stable, suggesting minimal toxicity.

[CONCLUSION] Our findings revealed that apatinib significantly suppressed tumor growth in these models, accompanied by a reduction in tumor microvascular density and Ki-67 expression, indicating its potential mechanism of action through inhibiting angiogenesis and tumor cell proliferation. These findings support its potential as a targeted therapy for tongue cancer and highlight the utility of PDX models for preclinical drug evaluation. Further studies with larger cohorts are warranted to validate these results.