目的：探讨全反式维甲酸（all-transretinoic acid，ATRA）和钝顶螺旋藻藻蓝蛋白（C-phycocyanin，C-PC）联合用药对人宫颈癌HeLa细胞繁殖和凋亡的影响及其诱导细胞凋亡可能的分子机制。 方法： 实验分4组：对照组，C-PC组，ATRA组，C-PC+ATRA联合用药组。MTT法检测ATRA和C-PC单独及联合用药对HeLa细胞增殖的影响并计算它们的IC50，TUNEL法检测单独及联合用药后HeLa细胞凋亡情况，免疫组化法检测Bcl-2的表达，Westren blotting法检测Caspase-3的表达。 结果： ATRA和C-PC均具有抑制HeLa细胞增殖的作用，IC50分别为（0.158± 0.036）mmol/L和（192.75± 5.79）μg/L。采用不同浓度的ATRA分别联合40或80 μg/L C-PC处理HeLa细胞，ATRA的IC50分别为（0.095±0.007）mmol/L和（0.062±0004）mmol/L，明显低于ATRA单独用药时的IC50值；当达到相同的抑制率时，联合C-PC用药可以显著降低ATRA的使用剂量。与对照组相比，两种药物单独用药增加了HeLa细胞凋亡水平（IOD C-PC=63.12, IOD ATRA=59.98， P <0.05）；当两种药物联合用药时，凋亡水平增加更加显著（IOD=89.52， P <0.01）。两药联合使用后HeLa细胞显著下调Bcl-2和上调Caspase-3的表达水平（均 P <0.01）。 结论： ATRA和C-PC联合用药可抑制HeLa细胞增殖和诱导其凋亡，其分子机制可能是通过抑制Bcl-2表达、促进Caspase-3表达来实现的。

Objective: To investigate the effects of all-transretinoic acid (ATRA) and C-phycocyanin (C-PC), either each alone or two in combination on cervical cancer cell growth and apoptosis in vitro . Methods: Immortalized human cervical cancer HeLa cells were treated with ATRA and C-CP, either each at various concentrations or two in various dose combinations. After treatment for 48 h, cell viability was assessed by MTT assay, apoptosis by TUNEL assay, and changes in Caspase-3 and Bcl-2 protein contents by Western blotting and immunohistochemistry staining, respectively. Results: C-PC and ATRA each alone significantly inhibited the growth of HeLa cells; and IC 50 was 0.158±0.036 mmol/L for C-CP and 192.75±5.79 μg/L for ATRA ( P <0.05). When ATRA was combined with C-PC, the IC 50 was significantly lower than that when ATRA was used alone. Compared with non-treatment control, C-PC and ATRA each alone induced significant HeLa cell apoptosis ( P <0.05), and in the apoptotic effect was more pronounced when C-PC and ATRA were used together ( P <0.01). ATRA and C-PC each alone significantly decreased Bcl-2 protein content ( P <0.01) but significantly increased Caspase-3 protein content ( P <0.01) in Hela cells, and both changes became more significant when ATRT and C-CP were used together ( P <0.01). Conclusion: C-PC combined with ATRA may induce cervical cancer cell apoptosis by down-regulation of Bcl-2 gene and up-regulation of Caspase-3 gene more effectively than each alone.

国家自然科学基金资助项目（No.81471546, No.81001346）；山东省医药卫生科技发展计划项目（No. 2011HZ023）；青岛市公共领域科技支撑计划项目（No. 2012-1-3-5-(4)-nsh）。