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首页> 外文期刊>Cellular Physiology and Biochemistry >Targeting CD44 by CRISPR-Cas9 in Multi-Drug Resistant Osteosarcoma Cells
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Targeting CD44 by CRISPR-Cas9 in Multi-Drug Resistant Osteosarcoma Cells

机译：通过CRISPR-Cas9在多药耐药骨肉瘤细胞中靶向CD44

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Background/Aims Drug resistance is the main difficulty for the current treatment for osteosarcoma. Cluster of differentiation 44 (CD44) is a receptor for hyaluronic acid (HA) and HA-binding has been proven to participate in various biological tumor activities, including tumor progression, metastasis and drug resistance. In this study, we aimed to determine the effects of CD44 on migration, invasion, proliferation, and the drug-sensitivity of osteosarcoma. Methods 96 human osteosarcoma tissues from 56 patients were collected to evaluate the expression of CD44 in osteosarcoma tissue by immunohistochemistry. CRISPR-Cas9 system was used to specifically silence CD44 in drug-resistant cell lines (KHOSR2 and U-2OSR2). The migration and invasion activities of cells was demonstrated by wound healing and transwell invasion assay. The proliferation speed of the cells was detected under 3D cell culture condition. Drug resistance of cells was detected by MTT and drug uptake assay. Results The immunohistochemistry results demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis, recurrence and drug resistance in patients with osteosarcoma. After knocking-out of CD44 by the CRISPR-Cas9 system, not only the migration and invasion activities of osteosarcoma cells were significantly inhibited, but the drug sensitivity was also enhanced. Conclusion CD44 silencing could inhibit the development of osteosarcoma migration, invasion, proliferation and ameliorate drug resistance to current treatment in osteosarcoma. This study applies new strategy to target CD44, which may improve the prognosis of osteosarcoma.
机译：背景/目的耐药性是目前骨肉瘤治疗的主要困难。分化簇44（CD44）是透明质酸（HA）的受体，并且HA结合已被证明参与各种生物肿瘤活动，包括肿瘤进展，转移和耐药性。在这项研究中，我们旨在确定CD44对骨肉瘤的迁移，侵袭，增殖和药物敏感性的影响。方法收集56例患者的96例人骨肉瘤组织，采用免疫组化方法检测CD44在骨肉瘤组织中的表达。 CRISPR-Cas9系统用于特异性沉默耐药细胞株（KHOSR2和U-2OSR2）中的CD44。通过伤口愈合和transwell侵袭试验证明了细胞的迁移和侵袭活性。在3D细胞培养条件下检测细胞的增殖速度。通过MTT和药物吸收测定法检测细胞的耐药性。结果免疫组织化学结果表明，高水平的CD44可能预示着骨肉瘤患者的不良生存率以及较高的转移，复发和耐药性潜力。通过CRISPR-Cas9系统敲除CD44后，不仅明显抑制了骨肉瘤细胞的迁移和侵袭活性，而且还增强了药物敏感性。结论CD44沉默可抑制骨肉瘤的发展，迁移，侵袭，增殖，改善目前对骨肉瘤的耐药性。这项研究将新的策略应用于CD44，可以改善骨肉瘤的预后。

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