Effects of insulin-like growth factor binding protein 3 on cell growth and tumorigenesis in oral squamous cell carcinoma.
Effects of insulin-like growth factor binding protein 3 on cell growth and tumorigenesis in oral squamous cell carcinoma.
复制标题
胰岛素样生长因子结合蛋白3对口腔鳞状细胞癌细胞生长和肿瘤发生的影响
DOI：
10.21037/tcr.2019.08.13
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发表时间：
2019-09
影响因子：
0.9
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Xu HY;Zhu DW;Zhong LP;Zhang ZY;Yang CZ;Yang X;Zhang P
本研究旨在探讨胰岛素样生长因子结合蛋白3（IGFBP 3）对口腔鳞癌（OSCC）细胞生物学行为及肿瘤发生的影响。方法分别用siRNA IGFBP 3、pcDNA 0 IGFBP 3和siRNA NC（阴性对照）转染口腔鳞癌HB 96、CAL 27和Tca 8113细胞。评估了异常IGFBP 3对细胞活力、凋亡和集落形成的影响。采用实时定量PCR（qRT-PCR）和蛋白质印迹分析分别测量IGFBP 3 mRNA和蛋白质水平。用表达IGFBP 3的慢病毒质粒转染HB 96和CAL 27细胞，然后移植到裸鼠中以监测异种移植瘤形成。结果50 pmol siRNA-IGFBP 3的转染效率最高。与非靶向阴性对照（NC）相比，IGFBP 3的瞬时沉默显著降低细胞活力，并增加细胞凋亡。过表达IGFBP 3促进细胞活力。此外，与NC组相比，细胞生长和集落形成均减少，而在稳定转染的细胞中凋亡增加。此外，沉默IGFBP 3在3周后抑制了裸鼠中的细胞活力和肿瘤形成，并且集落形成减少了裸鼠中的肿瘤发生，但促进了OSCC细胞中的细胞凋亡。结论IGFBP 3在口腔鳞癌细胞中具有促肿瘤发生作用，并可能是IGFBP 3在细胞生长中调控异常的一种机制。因此，IGFBP 3可能是一个潜在的治疗OSCC的治疗靶点。
Background This study was performed to investigate the effect of insulin-like growth factor binding protein 3 (IGFBP3) on the biological behavior of tumor cells and tumorigenesis of oral squamous cell carcinoma (OSCC). Methods OSCC HB96, CAL27, and Tca8113 cells were transfected with the following plasmids: siRNA-IGFBP3, pcDNA-0-IGFBP3, or siRNA-NC (negative control). The effect of aberrant IGFBP3 on cell viability, apoptosis, and colony formation was assessed. Quantitative real-time PCR (qRT-PCR) and western blot analysis were used to measure IGFBP3 mRNA and protein levels, respectively. HB96 and CAL27 cells were transfected with IGFBP3-expressing lentiviral plasmids and then transplanted into nude mice to monitor xenograft tumor formation. Results An optimal transfection efficiency was obtained with 50 pmol siRNA-IGFBP3. Transient silencing of IGFBP3 significantly reduced cell viability, and increased apoptosis in comparison with the non-targeting negative control (NC). Overexpressing IGFBP3 promoted cell viability. Additionally, in comparison with the NC group, both cell growth and colony formation were reduced, while apoptosis was elevated in stably transfected cells. Moreover, silencing IGFBP3 inhibited cell viability and tumor formation in nude mice after 3 weeks, and colony formation, diminished tumorigenesis in nude mice, but promoted cell apoptosis in OSCC cells. Conclusions Collectively, our study revealed a protumorigenic role for IGFBP3 in OSCC cancer cells, and demonstrated a potential mechanism for the dysregulation of IGFBP3 in cell growth. Therefore, IGFBP3 may be a potential therapeutic target for the treatment of OSCC.