Su Qi-Biao, Wang Lai-You, Wei Gui-Ning, Liao Li-Zhen, Zhao Jie, Liu Hong-Jun, Shi Yu-Long, Li Le-Ping, Li Chen-Sheng
College of Health Science, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
Oncol Lett. 2017 Dec;14(6):7759-7766. doi: 10.3892/ol.2017.7230. Epub 2017 Oct 20.
Livin is a novel member of the inhibitor of apoptosis protein family, which has been identified to be expressed in various malignancies and is suggested to be associated with poor prognostic significance. However, no data are available concerning the significance of livin in mid-distal rectal cancer. In the present study, livin expression, and its association with clinicopathological characteristics and prognosis was examined in patients with mid-distal rectal cancer. Apoptotic susceptibility, invasion capacity and chemosensitivity of LoVo cells were investigated using small interfering RNA (siRNA)-mediated knockdown of livin. It was revealed that livin was highly expressed in mid-distal rectal cancer tissues compared with the normal rectal mucosal tissues. Livin expression was associated with pathological grade, extent of invasion (T stage) and extent of lymph node metastasis (N stage) of tumor, contributing to poor prognosis of mid-distal rectal cancer following surgery. The data suggest that aggressive surgery should be applied in patients with mid-distal rectal cancer with high expression of livin. It was also revealed that knockdown of livin by siRNA increased the apoptotic rate, suppressed invasion of LoVo cells, and decreased the half-maximal inhibitory concentration of oxaliplatin and 5-fluorouracil by ~50% in LoVo cells significantly compared with control groups. The data suggested that a combination of downregulation of livin and anticancer drugs may significantly decrease the toxicity of anticancer drugs. Taken together, the present study indicated that livin may be a promising target in clinical therapy of mid-distal rectal cancer.
Livin是凋亡抑制蛋白家族的一个新成员，已被证实可在多种恶性肿瘤中表达，并提示其与不良预后相关。然而，关于Livin在中低位直肠癌中的意义尚无相关数据。在本研究中，对中低位直肠癌患者的Livin表达及其与临床病理特征和预后的关系进行了研究。使用小干扰RNA（siRNA）介导的Livin基因敲低，研究了LoVo细胞的凋亡敏感性、侵袭能力和化疗敏感性。结果显示，与正常直肠黏膜组织相比，Livin在中低位直肠癌组织中高表达。Livin表达与肿瘤的病理分级、浸润范围（T分期）和淋巴结转移范围（N分期）相关，提示其对中低位直肠癌术后预后不良有影响。数据表明，对于Livin高表达的中低位直肠癌患者应采取积极的手术治疗。研究还显示，与对照组相比，siRNA介导的Livin基因敲低可显著提高LoVo细胞的凋亡率，抑制其侵袭能力，并使奥沙利铂和5-氟尿嘧啶对LoVo细胞的半数抑制浓度降低约50%。数据提示，下调Livin与抗癌药物联合使用可能会显著降低抗癌药物的毒性。综上所述，本研究表明Livin可能是中低位直肠癌临床治疗中一个有前景的靶点。
