Department of Orthopedics, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, PR China.
Oncol Rep. 2012 Nov;28(5):1693-700. doi: 10.3892/or.2012.1992. Epub 2012 Aug 24.
Cyclooxygenase-2 (COX-2) is frequently overexpressed in human malignancies and plays a crucial role in tumorigenesis and cancer progression. The present study aimed to investigate the expression and clinical significance of COX-2 and survivin (SUV) in human osteosarcomas (OS), and explore the effects and molecular mechanisms of a selective COX-2 inhibitor NS-398 and SUV on tumor proliferation and apoptosis. Fifty cases of human OS and osteochondromas (OC) were collected. The expression of COX-2 and SUV was assessed using immunohistochemical assays in biopsy samples. MG-63 human OS cells were treated with different concentrations of NS-398, used to investigate their effects on cell proliferation and apoptosis. The recombinant small hairpin RNA adenovirus vector rAd5-SUV was constructed, and the effects and molecular mechanisms of knockdown of SUV on proliferation and apoptosis were evaluated in MG-63 cells. A subcutaneous xenograft tumor model was established, validating the effects of rAd5-SUV on tumor growth in vivo. Based on the results, the expression of COX-2 and SUV in OS showed a higher strong reactivity rate compared with OC (73.3 vs. 25.0%, P=0.001; 63.3 vs. 30.0%, P=0.02), but it did not correlate with the clinicopathological characteristics of OS. NS-398 inhibited proliferation, induced apoptosis and decreased the mRNA expression of COX-2 and SUV in MG-63 cells. Furthermore, adenovirus-mediated knockdown of SUV inhibited proliferation, induced apoptosis, reduced the expression of proliferating cell nuclear antigen (PCNA), increased the expression of caspase-3 (CAS-3) and slowed the growth of xenograft tumors in MG-63 cells. Taken together, the expression of COX-2 and SUV is closely correlated with human OS, and inhibition of COX-2 or knockdown of SUV suppresses tumor proliferation and induces apoptosis, suggesting that COX-2 may be involved in OS cell proliferation and apoptosis through SUV-mediated regulation of PCNA and CAS-3 expression, and provides a potential therapeutic strategy for the treatment of cancer.
环氧化酶-2（COX-2）在人类恶性肿瘤中常过度表达，在肿瘤发生和癌症进展中起关键作用。本研究旨在探讨COX-2和存活素（SUV）在人类骨肉瘤（OS）中的表达及其临床意义，并研究选择性 COX-2 抑制剂 NS-398 和 SUV 对肿瘤增殖和凋亡的影响及其分子机制。收集了 50 例人骨肉瘤和骨软骨瘤（OC）病例。采用免疫组织化学方法检测活检样本中 COX-2 和 SUV 的表达。用不同浓度的 NS-398 处理 MG-63 人骨肉瘤细胞，研究其对细胞增殖和凋亡的影响。构建重组短发夹 RNA 腺病毒载体 rAd5-SUV，并在 MG-63 细胞中评估 SUV 敲低对增殖和凋亡的影响及其分子机制。建立皮下异种移植肿瘤模型，验证 rAd5-SUV 对体内肿瘤生长的影响。基于研究结果，与 OC 相比，OS 中 COX-2 和 SUV 的表达具有更高的强反应率（73.3%比 25.0%，P=0.001；63.3%比 30.0%，P=0.02），但与 OS 的临床病理特征无关。NS-398 抑制 MG-63 细胞增殖，诱导凋亡，并降低 COX-2 和 SUV 的 mRNA 表达。此外，腺病毒介导的 SUV 敲低抑制增殖，诱导凋亡，降低增殖细胞核抗原（PCNA）的表达，增加半胱氨酸天冬氨酸蛋白酶-3（CAS-3）的表达，减缓 MG-63 细胞异种移植肿瘤的生长。综上所述，COX-2 和 SUV 的表达与人类 OS 密切相关，抑制 COX-2 或 SUV 敲低可抑制肿瘤增殖并诱导凋亡，提示 COX-2 可能通过 SUV 调节 PCNA 和 CAS-3 的表达参与 OS 细胞的增殖和凋亡，为癌症的治疗提供了一种潜在的治疗策略。
