Expression of Survivin Gene and Its Relationship with Clinical Multidrug Resistance in Osteosarcoma

Objective: To study the expression of survivin and its relationship with clinical multidrug resistance in osteosarcoma. Methods: By using immunohistochemistry (S-P) method, the expression of Survivin in osteosarcoma, osteochondroma and normal osseous tissue, and the expression of P-glycoprotein in osteosarcoma was detected. Results: Survivin positive expression rate was 65.71% in osteosarcoma, but no expression of Survivin was detectable in osteochondroma and normal osseous tissue. The positive expression rate of Survivin was significantly associated with Enneking clinical stages and histological typing (WHO), but no relationship was found among Survivin expression and age, sex and tumor location. The positive expression rate of P-glycoprotein was 45.71%. There was a significant correlation between Survivin and p-glycoprotein. Conclusion: Survivin overexpression was significantly associated with clinical multidrug resistance in osteosarcoma. It could be a potential target for treatment of osteosarcoma.

癌症相关成纤维细胞通过转移外泌体LncRNANEAT1促进骨肉瘤对TRAIL耐药性研究

目的探索癌症相关成纤维细胞(CAFs)通过转移外泌体长链非编码RNA NEAT1(LncRNANEAT1)促进骨肉瘤对肿瘤坏死因子相关凋亡诱导配体(TRAIL)耐药性机制。方法实时荧光定量PCR(qRT-PCR)检测骨肉瘤亲本细胞和TRAIL耐药细胞中LncRNANEAT1的表达水平;TUNEL实验检测敲低LncRNANEAT1对骨肉瘤细胞TRAIL耐药性影响;Western blot检测正常成纤维细胞(NFs)和CAFs中的Fibronectin和a-SMA蛋白表达;qRT-PCR检测NFs和CAFs中的LncRNANEAT1的表达。使用NFs和CAFs的条件培养基处理骨肉瘤细胞, TUNEL实验检测骨肉瘤细胞对TRAIL敏感性的变化, Western blot检测ROCK2蛋白的表达;使用LncBase数据库和双荧光素酶报告基因实验分析了与LncRNANEAT1和ROCK2潜在结合的miRNAs。结果与骨肉瘤亲本细胞相比, 骨肉瘤TRAIL耐药的细胞中LncRNANEAT1的表达显著增加。敲低LncRNANEAT1 TRAIL耐药性被逆转。与NFs相比, CAFs中fibronectin和α-SMA蛋白表达显著增加, LncRNANEAT1的表达也明显增加。CAFs条件培养基处理的骨肉瘤细胞对TRAIL敏感性下降, 且ROCK2蛋白表达增加。LncRNANEAT1可吸附miR-142-3p上调ROCK2的表达。结论 CAFs通过转移外泌体LncRNANEAT1吸附miR-142-3p进而上调ROCK2的表达, 增强骨肉瘤细胞对TRAIL的耐药性。