Zhang Ruijie, Yao Wei, Qian Pin, Li Yingjie, Jiang Chaowen, Ao Zhi, Qian Guisheng, Wang Changzheng, Wu Guoming, Li Jin, Ji Fuyun, Xu Jianping
Institute of Human Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Biomed Pharmacother. 2015 Apr;71:172-84. doi: 10.1016/j.biopha.2014.11.004. Epub 2015 Mar 5.
Contactin-1 (CNTN-1), a glycosyl phosphatidylinositol anchor neural cell adhesion molecule (ACAM), is thought to function not only in nervous system development but also in the invasion and metastasis of several tumours. To investigate whether CNTN-1 is involved in multidrug resistance (MDR) in lung adenocarcinoma, CNTN-1 expression was compared between MDR human lung adenocarcinoma A549/cisplatin (A549/DDP) cells and its progenitor A549 cells. The comparison showed that CNTN-1 expression in A549/DDP cells was significantly higher than in A549 cells both at the mRNA level and the protein level. In order to confirm the physiological function of the abnormal expression, lentivirus-mediated short hairpin RNA (shRNA) was used to silence CNTN-1. Cell cytotoxicity assay and cell apoptosis assay revealed that silencing CNTN-1 both in A549 cells and in A549/DDP cells not only rendered cells more sensitive to cisplatin than the negative control, but also increased the cisplatin-induced apoptosis. Metastasis and invasion assays demonstrated that CNTN-1 knockdown reduced metastasis and invasion but did not affect A549 or A549/DDP cell proliferation. To investigate whether the abnormal expression of CNTN-1 is associated with characteristics of patients with non-small cell lung cancer (NSCLC), immunohistochemistry was used to detect CNTN-1 expression in 143 tissue samples from NSCLC patients and the results showed that the degree of CNTN-1 expression positively correlated with lymphatic invasion in patients with lung adenocarcinoma who received adjuvant cisplatin- or carboplatin-based treatment after surgery. Thus, we concluded that CNTN-1 is closely related with MDR of lung adenocarcinoma. Additionally, CNTN-1 is a novel marker to predict chemotherapeutic efficacy of patients with lung adenocarcinoma, especially with regard to cisplatin- or carboplatin-based regimens.
接触蛋白-1（CNTN-1）是一种糖基磷脂酰肌醇锚定神经细胞粘附分子（ACAM），被认为不仅在神经系统发育中起作用，还在几种肿瘤的侵袭和转移中发挥作用。为了研究CNTN-1是否参与肺腺癌的多药耐药（MDR），比较了多药耐药的人肺腺癌A549/顺铂（A549/DDP）细胞与其亲本A549细胞中CNTN-1的表达。比较结果显示，A549/DDP细胞中CNTN-1的表达在mRNA水平和蛋白质水平上均显著高于A549细胞。为了证实异常表达的生理功能，使用慢病毒介导的短发夹RNA（shRNA）使CNTN-1沉默。细胞毒性试验和细胞凋亡试验表明，在A549细胞和A549/DDP细胞中沉默CNTN-1不仅使细胞比阴性对照对顺铂更敏感，而且增加了顺铂诱导的细胞凋亡。转移和侵袭试验表明，敲低CNTN-1可减少转移和侵袭，但不影响A549或A549/DDP细胞的增殖。为了研究CNTN-1的异常表达是否与非小细胞肺癌（NSCLC）患者的特征相关，采用免疫组织化学方法检测了143例NSCLC患者组织样本中CNTN-1的表达，结果显示，在术后接受顺铂或卡铂辅助治疗的肺腺癌患者中，CNTN-1的表达程度与淋巴侵袭呈正相关。因此，我们得出结论，CNTN-1与肺腺癌的多药耐药密切相关。此外，CNTN-1是预测肺腺癌患者化疗疗效的一个新标志物，尤其是对于基于顺铂或卡铂的治疗方案。
