Xu Chun-Sheng, Zheng Jian-Yong, Zhang Hai-Long, Zhao Hua-Dong, Zhang Jing, Wu Guo-Qiang, Wu Lin, Wang Qing, Wang Wei-Zhong, Zhang Jian
The State Key Laboratory of Cancer Biology, Department of Gastrointestinal Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
Asian Pac J Cancer Prev. 2012;13(7):3233-8. doi: 10.7314/apjcp.2012.13.7.3233.
Esophageal carcinoma (EC) is one of the most aggressive cancers with a poor prognosis. Understanding the molecular mechanisms underlying esophageal cancer progression is a high priority for improved EC diagnosis and prognosis. Recently, MSP58 was shown to behave as an oncogene in colorectal carcinomas and gliomas. However, little is known about its function in esophageal carcinomas. We therefore examined the effects of MSP58 knockdown on the growth of esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo in order to gain a better understanding of its potential as a tumor therapeutic target. We employed lentiviral-mediated small hairpin RNA (shRNA) to knock down the expression of MSP58 in the ESCC cell lines Eca-109 and EC9706 and demonstrated inhibition of ESCC cell proliferation and colony formation in vitro. Furthermore, flow cytometry and western blot analyses revealed that MSP58 depletion induced cell cycle arrest by regulating the expression of P21, CDK4 and cyclin D1. Notably, the downregulation of MSP58 significantly inhibited the growth of ESCC xenografts in nude mice. Our results suggest that MSP58 may play an important role in ESCC progression.
食管癌（EC）是最具侵袭性的癌症之一，预后较差。了解食管癌进展的分子机制是改善食管癌诊断和预后的当务之急。最近，MSP58在结直肠癌和神经胶质瘤中被证明具有癌基因的作用。然而，其在食管癌中的功能却知之甚少。因此，我们研究了敲低MSP58对食管鳞状细胞癌（ESCC）细胞体外和体内生长的影响，以便更好地了解其作为肿瘤治疗靶点的潜力。我们采用慢病毒介导的小发夹RNA（shRNA）来敲低ESCC细胞系Eca-109和EC9706中MSP58的表达，并证明其在体外抑制了ESCC细胞的增殖和集落形成。此外，流式细胞术和蛋白质印迹分析表明，MSP58的缺失通过调节P21、CDK4和细胞周期蛋白D1的表达诱导细胞周期停滞。值得注意的是，MSP58的下调显著抑制了裸鼠体内ESCC异种移植瘤的生长。我们的结果表明，MSP58可能在ESCC进展中发挥重要作用。
