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目的:探讨全反式维甲酸和藻蓝蛋白单独及联合用药对HeLa细胞生长的影响,并揭示两者联合用药对细胞周期和细胞凋亡影响的分子机制。方法:MTT法检测全反式维甲酸和藻蓝蛋白单独及联合用药对HeLa细胞生长的影响,原位杂交法检测用药前后细胞内CDK-4基因mRNA的表达情况,免疫组化法检测用药前后bcl-2基因的表达情况,TUNEL法检测用药前后细胞凋亡情况。结果:全反式维甲酸和藻蓝蛋白均具有抑制HeLa细胞生长的作用,当达到相同的抑制率时,联合藻蓝蛋白使用可以显著降低全反式维甲酸的使用剂量从而达到降低毒副作用的目的。两者联合用药可以显著降低CDK-4的表达量从而对HeLa细胞的细胞周期产生影响。两者联合用药可以显著下调bcl-2的表达水平从而引发细胞凋亡。结论:通过联合藻蓝蛋白,可以显著降低全反式维甲酸的使用剂量从而降低毒副作用。全反式维甲酸和藻蓝蛋白联合用药抑制HeLa细胞生长的分子机制可能是通过抑制CDK-4和bcl-2的表达来影响细胞周期并最终导致细胞凋亡。
OBJECTIVE: To investigate the effects of all-trans retinoic acid and phycocyanin on the growth of HeLa cells and to reveal the molecular mechanism of the combined effect of the two drugs on cell cycle and apoptosis. Methods: MTT assay was used to detect the effect of all-trans retinoic acid and phycocyanin alone or in combination on HeLa cell proliferation. The expression of CDK-4 mRNA was detected by in situ hybridization before and after treatment. bcl-2 gene expression, TUNEL assay before and after treatment of cell apoptosis. Results: All-trans retinoic acid and phycocyanin all inhibited the growth of HeLa cells. When the same inhibitory rate was reached, the combined use of phycocyanin could significantly reduce the dose of all-trans retinoic acid so as to reduce the toxic and side effects purpose. The combination of the two can significantly reduce the expression of CDK-4 and thus have an impact on the cell cycle of HeLa cells. The combination of the two can significantly down-regulate the expression of bcl-2 and induce apoptosis. Conclusion: The combination of phycocyanin can significantly reduce the use of all-trans retinoic acid dose and thus reduce the side effects. The molecular mechanism of the combination of all-trans retinoic acid and phycocyanin in inhibiting the growth of HeLa cells may affect the cell cycle and ultimately lead to apoptosis by inhibiting the expression of CDK-4 and bcl-2.