Chen W T, He R G, Liu X K, Zhou X J
Department of Oral and Maxillofacial Surgery, Shanghai Ninth Hospital, Shanghai Second Medical University, P. R. China.
Chin J Dent Res. 1999 Dec;2(3-4):25-30.
All-trans-retinoic acid (ATRA) and interferons (IFNs) have been proven to synergistically amplify growth inhibition and apoptosis in the tongue squamous carcinoma cell line (Tca8113). Nuclear retinoic acid receptor-beta (RAR beta) was the key gene that mediated retinoid activity for squamous carcinoma cells. In order to understand the mechanism of ATRA combined with IFN gamma inhibiting growth of Tca8113 cells, this investigation focused on RAR beta mRNA expression.
In this experiment, RT-PCR method was used to analyze the RAR beta expression level, and viable cell count assay was carried out for growth inhibition studies.
All-trans-retinoic acid (1 microM) and IFN gamma (1000 u/mL) inhibited cell growth by 39.2% and 44.4%, respectively. Synergistic inhibition of cell proliferation by 86.7% was found under combined treatment. The combination of suboptimal concentrations of ATRA (0.1 microM) with IFN gamma (1000 u/mL) showed a much stronger additive inhibitory effect on cell proliferation. ATRA (1 microM) and IFN gamma (1000 u/mL) increased RAR beta expression to 4 times and 3 times, respectively. The expression of RAR beta increased 12 times after treatment with combined ATRA and IFN gamma treatment.
These observations indicated that the use of combined ATRA and IFN may lead to enhanced antitumor effects. These results also suggested that ATRA and IFN mediated upregulating expression of RAR beta may play an important role in synergistic inhibition of proliferation in Tca8113 cells.
全反式维甲酸(ATRA)和干扰素(IFN)已被证明可协同增强舌鳞状癌细胞系(Tca8113)的生长抑制和凋亡作用。核维甲酸受体β(RARβ)是介导鳞状癌细胞维甲酸活性的关键基因。为了解ATRA联合IFNγ抑制Tca8113细胞生长的机制,本研究聚焦于RARβ mRNA表达。
本实验采用RT-PCR法分析RARβ表达水平,并进行活细胞计数测定以研究生长抑制情况。
全反式维甲酸(1μM)和IFNγ(1000 u/mL)分别抑制细胞生长39.2%和44.4%。联合处理时发现对细胞增殖的协同抑制率为86.7%。次优浓度的ATRA(0.1μM)与IFNγ(1000 u/mL)联合对细胞增殖表现出更强的相加抑制作用。ATRA(1μM)和IFNγ(1000 u/mL)分别使RARβ表达增加至4倍和3倍。ATRA与IFNγ联合处理后RARβ表达增加了12倍。
这些观察结果表明,联合使用ATRA和IFN可能导致增强的抗肿瘤作用。这些结果还表明,ATRA和IFN介导的RARβ表达上调可能在协同抑制Tca8113细胞增殖中起重要作用。