全反式维甲酸对肿瘤细胞生长的影响

The effects of All-Trans-Retinoic Acid on the growth of tumor cells

摘要:

为探究全反式维甲酸（All-Trans-Retinoic Acid，ATRA）对胰腺癌和骨肉瘤细胞生长的影响，本文采用较大浓度跨度的ATRA处理胰腺癌PANC-1和骨肉瘤U2OS细胞，并通过MTS法检测细胞活力.实验结果表明，20~100 μmol/L低浓度的ATRA可以促进胰腺癌细胞PANC-1的生长，相反，200 μmol/L高浓度ATRA则抑制其生长.在骨肉瘤细胞U2OS中，10~80 μmol/L低浓度ATRA可促进细胞生长而150~200 μmol/L高浓度ATRA则表现出对细胞生长的显著的抑制作用.两种细胞中，低浓度ATRA的促生长作用可被硼替佐米(Bortezmoib BTZ)抑制，而高浓度ATRA的抑制作用可被BTZ增强.低浓度ATRA与BTZ联合用药可降低凋亡前体蛋白Procaspase3的表达，表明联合用药有可能影响了细胞的凋亡途径.从不同浓度的ATRA对胰腺癌和骨肉瘤细胞生长的双面作用，提示ATRA的用药剂量对临床治疗的影响

Abstract:

In order to explore the effects of All-Trans-Retinoic Acid (ATRA) on the growth of pancreatic cancer and osteosarcoma cells, this study used a larger span of ATRA concentration to treat pancreatic cancer cells PANC-1 and osteosarcoma cells U2OS and cell viability was determined by MTS viability assay. The results indicated that ATRA at a low concentration of 20~100 μmol/L could promote the growth of PANC-1 cells, on the contrary, ATRA at a high concentration of 200 μmol/L inhibited their growth. In U2OS cells, a low concentration of 10~80 μmol/L ATRA could facilitate cell growth, while a high concentration of 150~200 μmol/L ATRA showed a significant inhibitory effect on cell growth. The growth-promoting effects of low concentration ATRA could be inhibited by Bortezomib（BTZ）, while the inhibitory effects of high concentration ATRA could be enhanced by BTZ. The combination of ATRA and BTZ at low concentration reduced the expression of the apoptotic precursor protein Procaspase3, suggesting that the combination might affect the apoptotic pathway. This is the first report for the double-sided effects of different concentrations of ATRA on the growth of pancreatic cancer and osteosarcoma cells, reminding us that more attention should be paid to the impact of ATRA dosage on clinical therapy.