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Survivin基因沉默增强口腔鳞状细胞癌细胞的放射敏感性。

Survivin silencing enhances radiosensitivity in oral squamous cell carcinoma cell.

作者信息

Sun H-B, Zheng H-Y, Yan X

机构信息

Department of Stomatology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2014;18(18):2678-86.

Abstract

OBJECTIVE

Survivin is a member of the inhibitor of apoptosis protein (IAP) family. It is overexpressed in most cancer tissues and induces resistance to radiation therapy. In this study, we investigated whether knockdown of survivin by siRNA could induce apoptosis and enhance radiosensitivity in oral squamous cell carcinoma cells (OSCC).

MATERIALS AND METHODS

Oral squamous cell carcinoma cell lines KB was subjected to radiotherapy, small interfering RNA (siRNA) targeting survivin was transfected into KB cells in vitro, then subjected to radiotherapy. After irradiation or/and siRNA transfection, viable and dead cells were counted to determine radiation sensitivity by MTT assay, proliferation by colony-forming ability and apoptosis was analyzed by flow cytometry. Tumor-bearing mice were irradiated with 6 Gy of 60 Co-γ radiator.

RESULTS

The results showed knockdown of survivin in KB cells showed reduced cell proliferation and increased number of radiation-induced apoptosis. Apoptosis was increased by survivin silencing alone and increased further in combination with irradiation. Colony formation was significantly reduced by survivin silencing in combination with irradiation.

CONCLUSIONS

Survivin silencing sensitizes KB cells toward irradiation. Survivin silencing in combination with radiation inhibits cell proliferation and colony formation significantly and increases apoptosis more than each single treatment alone. In addition, survivin silencing significantly enhanced inhibition of tumor growth and potentiated cell apoptosis by irradiation in KB xenografts. In conclusion, survivin silencing could enhance sensitivity of human KB cells to radiotherapy in vitro and in vivo.

摘要

目的

生存素是凋亡抑制蛋白(IAP)家族的成员。它在大多数癌症组织中过度表达,并诱导对放射治疗的抗性。在本研究中,我们调查了通过小干扰RNA(siRNA)敲低生存素是否能诱导口腔鳞状细胞癌细胞(OSCC)凋亡并增强其放射敏感性。

材料与方法

口腔鳞状细胞癌细胞系KB接受放射治疗,将靶向生存素的小干扰RNA(siRNA)体外转染至KB细胞,然后进行放射治疗。在照射或/和siRNA转染后,通过MTT法计数存活和死亡细胞以确定放射敏感性,通过集落形成能力检测增殖情况,并通过流式细胞术分析凋亡情况。用60Co-γ射线6 Gy照射荷瘤小鼠。

结果

结果显示,敲低KB细胞中的生存素可降低细胞增殖并增加辐射诱导的凋亡细胞数量。单独沉默生存素可增加凋亡,与照射联合时凋亡进一步增加。生存素沉默与照射联合可显著减少集落形成。

结论

沉默生存素可使KB细胞对照射敏感。生存素沉默与放射联合可显著抑制细胞增殖和集落形成,并比单独的每种治疗更能增加凋亡。此外,在KB异种移植瘤中,沉默生存素可显著增强照射对肿瘤生长的抑制并增强细胞凋亡。总之,沉默生存素可在体外和体内增强人KB细胞对放射治疗的敏感性。

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