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

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^－9 mol/L、10^－8 mol/L、10^－7 mol/L、10^－6 mol/L、10－5 mol/L）分别作用于MCF-7和MDA-MB-231细胞24 h、96 h和168 h后，用CCK-8方法检测细胞活性。用或不用GnRHa（10^－5 mol/L）处理96 h后，分别加入5-氟尿嘧啶（5-FU）或表阿霉素(EPI)作用24 h，用CCK-8法检测细胞抑制率。用RT-PCR检测GnRHa（10^－5 mol/L）作用168 h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^－5 mol/L）作用96 h后，5－FU和EPI对两种细胞的IC50不改变；GnRHa（10^－5 mol/L）不影响5－FU（MCF-7细胞0.5 g/L，MDA－MB－231细胞0.5 g/L）和EPI（MCF-7细胞1.2 mg/L,MDA－MB－231细胞0.8 mg/L）对两种细胞的抑制作用（P>0.05）。GnRHa（10^－5 mol/L）作用168 h后，MCF-7细胞的PCNA mRNA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，MDR1 mRNA有弱表达。GnRHa作用后，抑制了MDR1 mRNA表达。MDA-MB-231细胞GnRHa作用前后， MDR1 mRNA均无表达。结论：GnRHa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MDR1 mRNA表达水平，减弱MCF-7细胞的耐药性。

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

AIM: To investigate whether gonadotropin-releasing hormone analogue (GnRHa) affect the sensitivity 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 expression detected by RT- PCR. GnRHa did not suppress cell growth after GnRHa exposure. IC50 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.