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目的通过体内外实验探讨细胞周期蛋白(cyclinD1)与舌鳞状细胞癌对顺铂(CDDP)耐药细胞系(Tca8113/CDDP)耐药的相关性。方法通过脂质体将cyclinD1正义、反义寡核苷酸序列分别导入Tca8113/CDDP细胞内。用甲基噻唑基四唑(MTT)法检测转染细胞系和耐药细胞系体外生长增殖情况及对顺铂的敏感性。将被转染的细胞及Tca8113/CDDP细胞接种于裸鼠皮下,建立移植瘤模型,共18只,每组6只。给予顺铂腹腔注射治疗,观察移植瘤体积变化,绘制生长曲线;称取瘤重,计算抑瘤率;光镜下观察移植瘤组织病理学变化。结果转导mRNA3′cyclinD1反义寡核苷酸的Tca8113/CDDP细胞在动物体内外生长明显受到顺铂的抑制;裸鼠皮下移植瘤抑瘤率达74%(P<0.05),移植瘤重量较对照组和转导正义寡核苷酸序列组差异均有统计学意义(P<0.05);光镜下可见反义寡核苷酸组移植瘤坏死明显。结论cyclinD1基因的反义调控联合顺铂能抑制Tca8113/CDDP细胞的生长能力及体内移植瘤的生长。研究结果提示:抑制cyclinD1可能增加口腔鳞状细胞癌对顺铂的敏感度。
Objective To investigate the relationship between cyclinD1 and tongue squamous cell carcinoma (SCC) resistance to cisplatin (CDDP) resistant cell line (Tca8113 / CDDP) in vitro and in vivo. Methods The sense and antisense oligonucleotides of cyclinD1 were introduced into Tca8113 / CDDP cells respectively by liposome. Methyl thiazolyl tetrazolium (MTT) method was used to detect the growth and proliferation of transfected cell lines and drug-resistant cell lines in vitro and its sensitivity to cisplatin. Transfected cells and Tca8113 / CDDP cells were inoculated subcutaneously in nude mice to establish a xenograft tumor model, a total of 18, 6 mice in each group. Intraperitoneal injection of cisplatin was given to observe the volume of tumor xenografts changes and draw the growth curve; tumor weight was weighed, the inhibition rate was calculated; the histopathological changes were observed under light microscope. Results The growth of Tca8113 / CDDP cells transduced with antisense oligodeoxynucleotide 3’cyclinD1 was significantly inhibited by cisplatin in vivo and in vitro. The antitumor rate of subcutaneously transplanted tumor in nude mice was 74% (P <0.05) There was significant difference between the control group and the transduced sense oligonucleotide sequence group (P <0.05). The antitumor oligonucleotide group showed obvious necrosis of tumor xenografts. Conclusion The antisense regulation of cyclinD1 gene combined with cisplatin can inhibit the growth of Tca8113 / CDDP cells and the growth of xenografts in vivo. The results suggest that: inhibition of cyclinD1 may increase oral squamous cell carcinoma of cisplatin sensitivity.