School of Life Sciences and Technology, Tongji Univesity, Shanghai 200092, China.
Neoplasma. 2011;58(5):449-54. doi: 10.4149/neo_2011_05_449.
CD147, a widely expressed cell surface glycoprotein in cancer, is associated with tumor invasiveness and chemotherapy resistance. Recently, CD147 is also regarded as a potential therapeutic target for cancer therapy. The aim of the study was to investigate CD147 expression in non-small cell lung cancer (NSCLC), and evaluate its correlation with cisplatin-based chemotherapy resistance. In this study, we examined immunohistochemically the expression of CD147 in 118 advanced NSCLC cases treated with cisplatin-based chemotherapy, and then the association of CD147 expression with clinicopathological characteristics was analyzed. Furthermore, RNA interference approach was used to silence CD147 expression in a cisplatin-resistant human lung cancer cell line A549/DDP, and the inhibition effect of cisplatin on tumor cells was assayed by MTT. In the overall series, positive CD147 expression was observed in 101/118 (85.6%) cases. A membranous CD147 pattern was identified in 76/101 (75.2%) of CD147 positive tumors. CD147 membranous expression,but not the overall CD147 expression, was associated with poor response to cisplatin-based chemotherapies and a poor prognosis in advanced NSCLC patients. In vitro results showed that silencing CD147 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, our study indicated that membranous CD147 expression is a predictive factor of the response to cisplatin-based chemotherapies, and the use of CD147-targeted therapeutic adjuvants might be considered in the treatment of advanced NSCLC patients.
CD147 是一种广泛表达于癌症细胞表面的糖蛋白,与肿瘤侵袭性和化疗耐药性相关。最近,CD147 也被视为癌症治疗的潜在治疗靶点。本研究旨在探讨 CD147 在非小细胞肺癌(NSCLC)中的表达,并评估其与顺铂为基础的化疗耐药性的相关性。在本研究中,我们采用免疫组织化学方法检测了 118 例接受顺铂为基础化疗的晚期 NSCLC 病例中 CD147 的表达,并分析了 CD147 表达与临床病理特征的相关性。此外,我们还采用 RNA 干扰技术沉默了顺铂耐药的人肺癌细胞系 A549/DDP 中的 CD147 表达,并通过 MTT 法检测了顺铂对肿瘤细胞的抑制作用。在整个研究系列中,118 例病例中有 101 例(85.6%)CD147 阳性。在 101 例 CD147 阳性肿瘤中,有 76 例(75.2%)呈现膜性 CD147 表达模式。膜性 CD147 表达而非总 CD147 表达与晚期 NSCLC 患者对顺铂为基础化疗的反应不良和预后不良相关。体外研究结果表明,沉默 CD147 可增强顺铂对 A549/DDP 细胞的增殖抑制作用。综上所述,本研究表明膜性 CD147 表达是顺铂为基础化疗反应的预测因素,在治疗晚期 NSCLC 患者时可能考虑使用针对 CD147 的治疗性辅助药物。