小窝蛋白-1对洛伐他汀联合塞来昔布治疗宫颈癌的分子影响

Molecular Effect of Caveolin-1 on Lovastatin Combined with Celecoxib in the Treatment of Cervical Cancer

探讨洛伐他汀联合塞来昔布作用于宫颈癌细胞SiHa的关键分子及对下游信号分子的影响。分别用不同浓度的洛伐他汀和塞来昔布孵育宫颈癌细胞Si Ha,根据CCK-8试剂盒检测24 h的细胞增殖结果,计算两药的IC_(50)。用IC_(50)浓度的洛伐他汀和塞来昔布作用于SiHa,qPCR检测小窝蛋白-1的mRNA水平变化以及Akt、ERK1/2和STAT3的磷酸化水平。SiHa细胞经洛伐他汀和塞来昔布处理24 h后,IC_(50)值分别为25μmol/L和50μmol/L;洛伐他汀或塞来昔布单独处理Si Ha细胞24 h,均可从蛋白水平抑制小窝蛋白-1的表达;并且洛伐他汀可协同塞来昔布降低小窝蛋白-1引起的Akt、ERK1/2和STAT3信号分子磷酸化。洛伐他汀和塞来昔布联合应用下调宫颈癌细胞小窝蛋白-1的表达,并且可以显著性抑制下游信号分子的激活。

To investigate the effect of Lovastatin in combination with Celecoxib on key molecules of cervical cancer SiHa cells and downstream signal molecules. The cervical cancer SiHa cells were cultured with Lovastatin and Celecoxib in different concentrations, the result of cell proliferation of 24 h was examined based on CCK-8 kit, and IC50 values of two drugs were calculated. Then the SiHa cells were treated with Lovastatin and Celecoxib under the concentration of IC50. Using qPCR to detect the change of caveolin-1 mRNA levels and the phosphorylation level of Akt, ERK1/2 and STAT3. After 24 h treatment with Lovastatin and Celecoxib on the SiHa cells, the IC50 values were respectively 25μmol/L and 50μmol/L. When SiHa cells were treated by Lovastatin or Celecoxib separately for 24 h, they could inhibit the expression of caveolin-1 in the protein level. Besides, Lovastatin in combination with Celecoxib could reduce the phosphorylation of signaling molecules Akt, ERK1/2 and STAT3 caused by caveolin-1. Lovastatin in combination with Celecoxib down-regulate the expression of caveolin-1 of cervical cancer cells, and significantly inhibit the activation of downstream signaling molecules.