促性腺激素释放激素类似物对乳腺癌细胞株化疗敏感性的影响

Effects of gonadotropin-releasing hormone analogue on sensitivity of breast cancer cells to 5-FU and epirubicin in vitro

目的:探讨促性腺激素释放激素类似物(GnRHa)对乳腺癌细胞株(MCF-7和MDA-MB-231)化疗敏感性的影响。方法:不同浓度的GnRHa(曲普瑞林,triptorelin)(10-9mol/L、10-8mol/L、10-7mol/L、10-6mol/L、10-5mol/L)分别作用于MCF-7和MDA-MB-231细胞24h、96h和168h后,用CCK-8方法检测细胞活性。用或不用GnRHa(10-5mol/L)处理96h后,分别加入5-氟尿嘧啶(5-FU)或表阿霉素(EPI)作用24h,用CCK-8法检测细胞抑制率。用RT-PCR检测GnRHa(10-5mol/L)作用168h后GnRH受体、PCNA和MDR1 mRNA表达水平。结果:不同浓度GnRHa作用不同的时间后对乳腺癌细胞活性无影响。GnRHa(10-5mol/L)作用96h后,5-FU和EPI对两种细胞的IC50不改变;GnRHa(10-5mol/L)不影响5-FU(MCF-7细胞0.5g/L,MDA-MB-231细胞0.5g/L)和EPI(MCF-7细胞1.2mg/L,MDA-MB-231细胞0.8mg/L)对两种细胞的抑制作用(P>0.05)。GnRHa(10-5mol/L)作用168h后,MCF-7细胞的PCNAmRNA表达无改变。而在MDA-MB-231细胞,PCNA表达升高,差别有统计学意义(P<0.05)。在MCF-7对照组中,MDR1mRNA有弱表达。GnRHa作用后,抑制了MDR1mRNA表达。MDA-MB-231细胞GnRHa作用前后,MDR1mRNA均无表达。结论:Gn-RHa不影响乳腺癌细胞株对5-FU和EPI的敏感性。GnRHa可能通过下调MDR1mRNA表达水平,减弱MCF-7细胞的耐药性。

AIM： To investigate whether gonadotropin -releasing hormone analogue （GnRHa） affect the sen- sitivity of breast cancer cells to 5 - FU and epirubicin in vitro. METHODS ： Two breast cancer cell lines （ MCF - 7 and MDA - MB - 231 ） were treated with different concentrations of GnRH analogue, triptorelin acetate, or with a GnRHa ＋ 5 - FU or GnRHa ＋ epirubicin. The cellular growth profiles were determined by CCK - 8. The mRNA levels of GnRH receptor, PCNA and MDR1 were measured by RT - PCR. RESULTS： Both cell lines had positive GnRH receptor mRNA ex- pression detected by RT - PCR. GnRHa did not suppress cell growth after GnRHa exposure. IC50 of 5 - FU and epirubicin was not changed in the presence of GnRHa. Suppression of cell growth by the exposure to 5 - FU and epirubicin was not changed in the presence of GnRHa. GnRHa treatment up - regulated PCNA mRNA expression in MDA - MB - 231 cells but not in MCF - 7 cells. The expression of MDR1 mRNA was down - regulated by GnRHa in MCF - 7 cell lines. No MDR1 mRNA expression in MDA -MB -231 cells was observed. CONCLUSION： The present data suggest that GnRH analogue （ triptorelin acetate） does not affect the sensitivity of breast cancer cell lines MCF - 7 and MDA - MB - 231 to 5 - FU and epirubicin. GnRHa may decrease the drug resistance by down - regulating MDR1 mRNA expression.