Department of Orthopedics, Second Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, PR China.
Mol Med Rep. 2013 Jul;8(1):168-72. doi: 10.3892/mmr.2013.1484. Epub 2013 May 20.
Osteosarcoma is the most common form of primary malignant bone tumor. Patients who are insensitive to chemotherapy treatment often have a poor prognosis. According to our previous study, recombinant adenovirus (Myc-AS) in combination with caffeine enhances the induction of apoptosis and the chemotherapeutic effects of cisplatin (CDDP) in MG-63 osteosarcoma cells. The present study aimed to investigate the combinational effects of the small interfering RNAs (siRNAs) c-myc and Bmi-1 on the growth and chemosensitivity of MG-63 osteosarcoma cells. The results indicated that the cell growth inhibition rates of MG-63 cells gradually increased with increasing concentrations of CDDP (P<0.05). This observation was consistent in the single and combined siRNA groups. At a concentration of 5.0 µg/ml CDDP, the growth inhibition rates were 53.3±5.2, 42.7±6.3 and 40.9±4.7% in the combined, c-myc and Bmi-1 siRNA groups, respectively. The cell growth inhibition rate in the combined siRNA group was higher than that observed in the two single siRNA groups (P<0.05). The cell apoptotic rate was 37.3±4.9% in the combined siRNA group, which was significantly higher than that observed in the c-myc (24.8±5.6%) and Bmi-1 siRNA groups (22.7±6.1%; P<0.05). These results suggest that the chemosensitivity of MG-63 cells to CDDP may be markedly enhanced in the siRNA combination group. A decrease in cell proliferation and increased cell apoptosis were also observed in the siRNA combination group. The present study may provide novel insights to further elucidate the pathogenesis and drug resistance mechanisms involved in osteosarcoma. It may also improve our understanding of the underlying mechanisms involved in chemotherapeutic sensitivity, and thus aid the development of future therapeutic strategies for the treatment of osteosarcoma.
骨肉瘤是最常见的原发性恶性骨肿瘤。对化疗治疗不敏感的患者预后往往较差。根据我们之前的研究,重组腺病毒(Myc-AS)联合咖啡因增强了 MG-63 骨肉瘤细胞中顺铂(CDDP)诱导的细胞凋亡和化疗效果。本研究旨在探讨微小干扰 RNA(siRNA)c-myc 和 Bmi-1 对 MG-63 骨肉瘤细胞生长和化疗敏感性的联合作用。结果表明,随着 CDDP 浓度的增加,MG-63 细胞的生长抑制率逐渐增加(P<0.05)。在单独和联合 siRNA 组中均观察到了这一观察结果。在 5.0 µg/ml CDDP 浓度下,联合 siRNA 组、c-myc siRNA 组和 Bmi-1 siRNA 组的细胞生长抑制率分别为 53.3±5.2%、42.7±6.3%和 40.9±4.7%。联合 siRNA 组的细胞生长抑制率高于两个单独 siRNA 组(P<0.05)。联合 siRNA 组的细胞凋亡率为 37.3±4.9%,明显高于 c-myc siRNA 组(24.8±5.6%)和 Bmi-1 siRNA 组(22.7±6.1%)(P<0.05)。这些结果表明,MG-63 细胞对 CDDP 的化疗敏感性可能在 siRNA 联合组中显著增强。在 siRNA 联合组中还观察到细胞增殖减少和细胞凋亡增加。本研究可能为进一步阐明骨肉瘤的发病机制和耐药机制提供新的见解。它还可能加深我们对化疗敏感性相关潜在机制的理解,从而有助于开发治疗骨肉瘤的未来治疗策略。