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Sun, Yiping, Xin, Yuqi, He, Yuanqiao, Liu, Junyao, HU, Xiaoping. (1404). Antitumor Effects of Apatinib on Tongue Cancer in Patient-Derived Xenograft Models. سامانه مدیریت نشریات علمی, 51(2), 145-153. doi: 10.30476/ijms.2025.106422.4059
Yiping Sun; Yuqi Xin; Yuanqiao He; Junyao Liu; Xiaoping HU. "Antitumor Effects of Apatinib on Tongue Cancer in Patient-Derived Xenograft Models". سامانه مدیریت نشریات علمی, 51, 2, 1404, 145-153. doi: 10.30476/ijms.2025.106422.4059
Sun, Yiping, Xin, Yuqi, He, Yuanqiao, Liu, Junyao, HU, Xiaoping. (1404). 'Antitumor Effects of Apatinib on Tongue Cancer in Patient-Derived Xenograft Models', سامانه مدیریت نشریات علمی, 51(2), pp. 145-153. doi: 10.30476/ijms.2025.106422.4059
Sun, Yiping, Xin, Yuqi, He, Yuanqiao, Liu, Junyao, HU, Xiaoping. Antitumor Effects of Apatinib on Tongue Cancer in Patient-Derived Xenograft Models. سامانه مدیریت نشریات علمی, 1404; 51(2): 145-153. doi: 10.30476/ijms.2025.106422.4059

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

Iranian Journal of Medical Sciences
مقاله 7، دوره 51، شماره 2، اردیبهشت 2026، صفحه 145-153    اصل مقاله (2.58 M)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/ijms.2025.106422.4059
نویسندگان
Yiping Sun1، 2، 3؛ Yuqi Xin4؛ Yuanqiao He5؛ Junyao Liu1، 2، 3؛ Xiaoping HU* 1، 2، 3
1The Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
2Jiangxi Province Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi, China
3Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, Jiangxi, China
4Department of Stomatology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
5Center of Laboratory Animal Science, Nanchang University, Nanchang, Jiangxi, China
چکیده
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 post hoc 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 mm³ vs. Control 800.98±581.05 mm³, 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.

تازه های تحقیق

Yiping Sun (Google Scholar)

Xiaoping Hu (Google Scholar)

کلیدواژه‌ها
Apatinib؛ Xenograft model antitumor assay؛ Tongue neoplasms؛ Platelet endothelial cell adhesion molecule-1؛ Ki-67 antigen
مراجع
  1. Sakr Y, Hamdy O, Eldeghedi M, Abdelaziz R, Med Sidi El Moctar E, Alharazin M, et al. Shifting epidemiology trends in tongue cancer: A retrospective cohort study. Cancers (Basel). 2023;15:5680. doi: 10.3390/cancers15235680. PubMed PMID: 38067383; PubMed Central PMCID: PMC10705286.
  2. Li Y, Chu C, Hu C. Effects of surgery on survival of patients aged 75 years or older with oral tongue squamous cell carcinomas. Sci Rep. 2021;11:6003. doi: 10.1038/s41598-021-85647-y. PubMed PMID: 33727684; PubMed Central PMCID: PMC7966770.
  3. Abdolahi S, Ghazvinian Z, Muhammadnejad S, Saleh M, Asadzadeh Aghdaei H, Baghaei K. Patient-derived xenograft (PDX) models, applications and challenges in cancer research. J Transl Med. 2022;20:206. doi: 10.1186/s12967-022-03405-8. PubMed PMID: 35538576; PubMed Central PMCID: PMC9088152.
  4. Yoshida GJ. Applications of patient-derived tumor xenograft models and tumor organoids. J Hematol Oncol. 2020;13:4. doi: 10.1186/s13045-019-0829-z. PubMed PMID: 31910904; PubMed Central PMCID: PMC6947974.
  5. Xu X, Kumari R, Zhou J, Chen J, Mao B, Wang J, et al. A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology. PLoS One. 2023;18:e0279821. doi: 10.1371/journal.pone.0279821. PubMed PMID: 36602988; PubMed Central PMCID: PMC9815646.
  6. Fathi Maroufi N, Rashidi MR, Vahedian V, Akbarzadeh M, Fattahi A, Nouri M. Therapeutic potentials of apatinib in cancer treatment: Possible mechanisms and clinical relevance. Life Sci. 2020;241:117106. doi: 10.1016/j.lfs.2019.117106. PubMed PMID: 31786193.
  7. Wang L, Li W, Liu YG, Zhang C, Gao WN, Gao LF. Clinical efficacy and safety of bevacizumab, apatinib, and recombinant human endothelial inhibitor in the treatment of advanced gastric cancer. J Oncol. 2022;2022:6189833. doi: 10.1155/2022/6189833. PubMed PMID: 35251174; PubMed Central PMCID: PMC8894022.
  8. Li H, Huang H, Zhang T, Feng H, Wang S, Zhang Y, et al. Apatinib: A novel antiangiogenic drug in monotherapy or combination immunotherapy for digestive system malignancies. Front Immunol. 2022;13:937307. doi: 10.3389/fimmu.2022.937307. PubMed PMID: 35844616; PubMed Central PMCID: PMC9276937.
  9. Zhao L, Peng Y, He S, Li R, Wang Z, Huang J, et al. Apatinib induced ferroptosis by lipid peroxidation in gastric cancer. Gastric Cancer. 2021;24:642-54. doi: 10.1007/s10120-021-01159-8. PubMed PMID: 33544270.
  10. Li Z, Zhou X, Wang S, Shi L, Meng R, Dai X, et al. The efficacy and safety of apatinib in patients with heavily pretreated end-stage cancer: a retrospective study. Transl Cancer Res. 2023;12:904-12. doi: 10.21037/tcr-22-2080. PubMed PMID: 37180651; PubMed Central PMCID: PMC10174995.
  11. Ju W-t, Xia R-h, Zhu D-w, Dou S-j, Zhu G-p, Dong M-j, et al. A pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma. Nat Commun. 2022;13:5378. doi: 10.1038/s41467-022-33080-8.
  12. Xin Y, Li S, Jiang Q, Hu F, He Y, Zhang J. Establishment of a jaw fibrosarcoma patient-derived xenograft and evaluation of the tumor suppression efficacy of plumbagin against jaw fibrosarcoma. Front Oncol. 2020;10:1479. doi: 10.3389/fonc.2020.01479. PubMed PMID: 32974176; PubMed Central PMCID: PMC7481444.
  13. Hu F, Guo L, Yu J, Dai D, Xiong Y, He Y, et al. Using patient-derived xenografts to explore the efficacy of treating head-and-neck squamous cell carcinoma with anlotinib. Pathol Oncol Res. 2021;27:1610008. doi: 10.3389/pore.2021.1610008. PubMed PMID: 34955687; PubMed Central PMCID: PMC8696349.
  14. Kvietkauskas M, Zitkute V, Leber B, Strupas K, Stiegler P, Schemmer P. Dietary melatonin and glycine decrease tumor growth through antiangiogenic activity in experimental colorectal liver metastasis. Nutrients. 2021;13:2035. doi: 10.3390/nu13062035. PubMed PMID: 34199311; PubMed Central PMCID: PMC8231877.
  15. Chen L, Pan X, Zhang YH, Hu X, Feng K, Huang T, et al. Primary tumor site specificity is preserved in patient-derived tumor xenograft models. Front Genet. 2019;10:738. doi: 10.3389/fgene.2019.00738. PubMed PMID: 31456818; PubMed Central PMCID: PMC6701289.
  16. Guo S, Gao S, Liu R, Shen J, Shi X, Bai S, et al. Oncological and genetic factors impacting PDX model construction with NSG mice in pancreatic cancer. FASEB J. 2019;33:873-84. doi: 10.1096/fj.201800617R. PubMed PMID: 30091943.
  17. Xu W, Zhao ZY, An QM, Dong B, Lv A, Li CP, et al. Comprehensive comparison of patient-derived xenograft models in hepatocellular carcinoma and metastatic liver cancer. Int J Med Sci. 2020;17:3073-81. doi: 10.7150/ijms.46686. PubMed PMID: 33173428; PubMed Central PMCID: PMC7646096.
  18. Maletzki C, Bock S, Fruh P, Macius K, Witt A, Prall F, et al. NSG mice as hosts for oncological precision medicine. Lab Invest. 2020;100:27-37. doi: 10.1038/s41374-019-0298-6. PubMed PMID: 31409886.
  19. Fan X, Wu L, Cheng T, Lv W, Tian J, Tao J, et al. Oroxylin A may promote cell apoptosis and inhibit epithelial-mesenchymal transition in endometrial cancer, associated with the ERβ/PI3K/AKT pathway. Sci Rep. 2025;15:12225. doi: 10.1038/s41598-025-97122-z. PubMed PMID: 40211010; PubMed Central PMCID: PMC11986019.
  20. Al-Ostoot FH, Salah S, Khamees HA, Khanum SA. Tumor angiogenesis: Current challenges and therapeutic opportunities. Cancer Treat Res Commun. 2021;28:100422. doi: 10.1016/j.ctarc.2021.100422. PubMed PMID: 34147821.
  21. Xie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 2020;5:22. doi: 10.1038/s41392-020-0116-z. PubMed PMID: 32296018; PubMed Central PMCID: PMC7082344.
  22. Liu Y, Long L, Zhang F, Hu X, Zhang J, Hu C, et al. Microneedle-mediated vascular endothelial growth factor delivery promotes angiogenesis and functional recovery after stroke. J Control Release. 2021;338:610-22. doi: 10.1016/j.jconrel.2021.08.057. PubMed PMID: 34481025.
  23. Kang R, Song M, Fang Z, Liu K. Nano-composite hydrogels of Cu-Apa micelles for anti-vasculogenic mimicry. J Drug Target. 2023;31:166-78. doi: 10.1080/1061186x.2022.2115047. PubMed PMID: 35993258.
  24. Tao K, Chen C, Xu G, Tao F, He M. Low-dose apatinib optimizes the vascular normalization and enhances the antitumor effect of PD-1 inhibitor in gastric cancer. Transl Cancer Res. 2024;13:4290-300. doi: 10.21037/tcr-23-2328. PubMed PMID: 39262493; PubMed Central PMCID: PMC11385532.
  25. Liu X, Xu J, Li F, Liao Z, Ren Z, Zhu L, et al. Efficacy and safety of the VEGFR2 inhibitor apatinib for metastatic soft tissue sarcoma: Chinese cohort data from NCT03121846. Biomed Pharmacother. 2020;122:109587. doi: 10.1016/j.biopha.2019.109587. PubMed PMID: 31786466.
  26. Tenyi A, Milutinović A, Nemeth L. Expression of CD31, CD34, and smooth muscle actin (SMA) in endothelial cells of dental pulp vessels. Biomol Biomed. 2023;24:821-6. doi: 10.17305/bb.2023.9988. PubMed PMID: 38153414; PubMed Central PMCID: PMC11293224.
  27. Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983;31:13-20. doi: 10.1002/ijc.2910310104. PubMed PMID: 6339421.
  28. Schwiebs A, Faqar-Uz-Zaman F, Herrero San Juan M, Radeke HH. S1P lyase regulates intestinal stem cell quiescence via Ki-67 and FOXO3. Int J Mol Sci. 2021;22:5682. doi: 10.3390/ijms22115682. PubMed PMID: 34073605; PubMed Central PMCID: PMC8198365.
  29. Lei HJ, Wang SY, Chau IY, Li AF, Chau YP, Hsia CY, et al. Hepatoma upregulated protein and Ki-67 expression in resectable hepatocellular carcinoma. J Chin Med Assoc. 2021;84:623-32. doi: 10.1097/jcma.0000000000000540. PubMed PMID: 33883465.
  30. Li Z, Li F, Pan C, He Z, Pan X, Zhu Q, et al. Tumor cell proliferation (Ki-67) expression and its prognostic significance in histological subtypes of lung adenocarcinoma. Lung Cancer. 2021;154:69-75. doi: 10.1016/j.lungcan.2021.02.009. PubMed PMID: 33626488.
  31. Atrash S, Robinson M, Taneja A, Paul B, Cassetta K, Ndiaye A, et al. Bone marrow Ki-67 index is of prognostic value in newly diagnosed multiple myeloma. Eur J Haematol. 2023;111:373-81. doi: 10.1111/ejh.14016. PubMed PMID: 37311695.
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